Skip to main content

The Role of TRP Ion Channels in Testicular Function

  • Chapter
  • First Online:
Transient Receptor Potential Channels

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 704))

Abstract

Transient receptor potential (TRP) proteins are homologues of Drosophila transient receptor potential ion channels first identified in the photo receptors and reported to be involved in calcium entry following calcium store depletion during photo transduction. TRP is a large super family divided in several families including the TRPC (Canonical) family, the TRPV (Vanilloid) family, the TRPM (Melastatin) family, the TRPP (Polycystin) family, the TRPML (Mucolipin) family, the TRPA (Ankyrin) family, and the TRPN (NOMPC) family. TRP proteins are six transmembrane ion channels and act as components of multimeric complexes which allow cation entry either after internal calcium depletion or in response to receptor stimulation. TRP ion channels have been reported to act as molecular sensors of environment. Trp genes are expressed in a wide range of tissues including testis. In addition to this TRP proteins have also been detected in mature sperm from a number of species including humans. TRP may be involved in regulating calcium dependent functions of sperm including motility, capacitation, and acrosome reaction. Here we review the available information about TRP proteins reported in the sperm, as well as in other cells/tissue systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Yanagimachi R (1994) Mammalian fertilization. In: Knobil E, Neill JD (ed) The physiology of reproduction. Raven Press, New York, NY, pp. 189–317

    Google Scholar 

  2. Abou-haila A, Tulsiani DR (2009) Signal transduction pathways that regulate sperm capacitation and the acrosome reaction. Arch Biochem Biophys 485:72–81

    CAS  PubMed  Google Scholar 

  3. Wolf DE, Hagopian SS, Ishijima S (1986) Changes in sperm plasma membrane lipid diffusibility after hyperactivation during in vitro capacitation in the mouse. J Cell Biol 102:1372–1377

    CAS  PubMed  Google Scholar 

  4. Zeng Y, Clark EN, Florman HM (1995) Sperm membrane potential: hyperpolarization during capacitation regulates zona pellucida-dependent acrosomal secretion. Dev Biol 171:554–563

    CAS  PubMed  Google Scholar 

  5. Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA, Pan D, Olds-Clarke P, Kopf GS (1995) Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development 121:1139–1150

    CAS  PubMed  Google Scholar 

  6. White DR, Aitken RJ (1989) Relationship between calcium, cyclic AMP, ATP, and intracellular pH and the capacity of hamster spermatozoa to express hyperactivated motility. Gamete Res 22:163–177

    CAS  PubMed  Google Scholar 

  7. Fraser LR (1990) Adenosine and its analogues, possibly acting at A2 receptors, stimulate mouse sperm fertilizing ability during early stages of capacitation. J Reprod Fertil 89: 467–476

    CAS  PubMed  Google Scholar 

  8. Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, Kopf GS (1995) Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development 121:1129–1137

    CAS  PubMed  Google Scholar 

  9. Naz RK, Ahmad K, Kumar R (1991) Role of membrane phosphotyrosine proteins in human spermatozoal function. J Cell Sci 99:157–165

    CAS  PubMed  Google Scholar 

  10. Naz RK, Rajesh PB (2004) Role of tyrosine phosphorylation in sperm capacitation/acrosome reaction. Reprod Biol Endocrinol 2:75

    PubMed Central  PubMed  Google Scholar 

  11. Babcock DF, Pfeiffer DR (1987) Independent elevation of cytosolic [Ca2+] and pH of mammalian sperm by voltage-dependent and pH-sensitive mechanisms. J Biol Chem 262:15041–15047

    CAS  PubMed  Google Scholar 

  12. Babcock DF, Bosma MM, Battaglia DE, Darszon A (1992) Early persistent activation of sperm K+ channels by the egg peptide speract. Proc Natl Acad Sci USA 89:6001–6005

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Garcia-Soto J, Darszon A (1985) High pH-induced acrosome reaction and Ca2+ uptake in sea urchin sperm suspended in Na+-free seawater. Dev Biol 110:338–345

    CAS  PubMed  Google Scholar 

  14. Labarca P, Santi C, Zapata O, Morales E (1996) Beltr’an,C, Li’evano,A, Darszon, A: a cAMP regulated K+-selective channel from the sea urchin sperm plasma membrane. Dev Biol 174:271–280

    CAS  PubMed  Google Scholar 

  15. Lee HC, Garbers DL (1986) Modulation of the voltage-sensitive Na+/H+ exchange in sea urchin spermatozoa through membrane potential changes induced by the egg peptide speract. J Biol Chem 261:16026–16032

    CAS  PubMed  Google Scholar 

  16. Silvestroni L, Menditto A (1989) Calcium uptake in human spermatozoa: characterization and mechanisms. Arch Androl 23:87–96

    CAS  PubMed  Google Scholar 

  17. Spira B, Breitbart H (1992) The role of anion channels in the mechanism of acrosome reaction in bull spermatozoa. Biochim Biophys Acta 1109:65–73

    CAS  PubMed  Google Scholar 

  18. Wistrom CA, Meizel S (1993) Evidence suggesting involvement of a unique human sperm steroid receptor/Cl– channel complex in the progesterone-initiated acrosome reaction. Dev Biol 159:679–690

    CAS  PubMed  Google Scholar 

  19. Wong PY, Lee WM (1983) Potassium movement during sodium-induced motility initiation in the rat caudal epididymal spermatozoa. Biol Reprod 28:206–212

    CAS  PubMed  Google Scholar 

  20. Florman HM, Corron ME, Kim TD, Babcock DF (1992) Activation of voltage-dependent calcium channels of mammalian sperm is required for zona pellucida-induced acrosomal exocytosis. Dev Biol 152:304–314

    CAS  PubMed  Google Scholar 

  21. Breitbart H, Rubinstein S, Nass-Arden L (1985) The role of calcium and Ca2+-ATPase in maintaining motility in ram spermatozoa. J Biol Chem 260:11548–11553

    CAS  PubMed  Google Scholar 

  22. Chinoy NJ, Verma RJ, Patel KG (1983) Effect of calcium on sperm motility of cauda epididymis in vitro. Acta Eur Fertil 14:421–423

    CAS  PubMed  Google Scholar 

  23. Davis BK (1978) Effect of calcium on motility and fertilization by rat spermatozoa in vitro. Proc Soc Exp Biol Med 157:54–56

    CAS  PubMed  Google Scholar 

  24. Gorus FK, Finsy R, Pipeleers DG (1982) Effect of temperature, nutrients, calcium, and cAMP on motility of human spermatozoa. Am J Physiol 242:C304–C311

    CAS  PubMed  Google Scholar 

  25. Hoskins DD, Brandt H, Acott TS (1978) Initiation of sperm motility in the mammalian epididymis. Fed Proc 37:2534–2542

    CAS  PubMed  Google Scholar 

  26. Iwasa F, Shimizu H, Mohri H (1981) Effects of Ca2+ and Mg2+ on motility of sea urchin spermatozoa. Experientia 37:861–862

    CAS  PubMed  Google Scholar 

  27. Morton BE, Sagadraca R, Fraser C (1978) Sperm motility within the mammalian epididymis: species variation and correlation with free calcium levels in epididymal plasma. Fertil Steril 29:695–698

    CAS  PubMed  Google Scholar 

  28. Nelson L, Gardner ME, Young MJ (1982) Regulation of calcium distribution in bovine sperm cells: cytochemical evidence for motility control mechanisms. Cell Motil 2:225–242

    CAS  PubMed  Google Scholar 

  29. Lee WM, Tsang AY, Wong PY (1981) Effects of divalent and lanthanide ions on motility initiation in rat caudal epididymal spermatozoa. Br J Pharmacol 73:633–638

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Anand SR, Atreja SK, Chauhan MS, Behl R (1989) In vitro capacitation of goat spermatozoa. Indian J Exp Biol 27:921–924

    CAS  PubMed  Google Scholar 

  31. Singh JP, Babcock DF, Lardy HA (1978) Increased calcium-ion influx is a component of capacitation of spermatozoa. Biochem J 172:549–556

    PubMed Central  CAS  PubMed  Google Scholar 

  32. Hong CY, Chiang BN, Turner P (1984) Calcium ion is the key regulator of human sperm function. Lancet 2:1449–1451

    CAS  PubMed  Google Scholar 

  33. Summers RG, Talbot P, Keough EM, Hylander BL, Franklin LE (1976) Ionophore A23187 induces acrosome reactions in sea urchin and guinea pig spermatozoa. J Exp Zool 196: 381–385

    CAS  PubMed  Google Scholar 

  34. Thomas P, Meizel S (1988) An influx of extracellular calcium is required for initiation of the human sperm acrosome reaction induced by human follicular fluid. Gamete Res 20:397–411

    CAS  PubMed  Google Scholar 

  35. Cox T, Peterson RN (1989) Identification of calcium conducting channels in isolated boar sperm plasma membranes. Biochem Biophys Res Commun 161:162–168

    CAS  PubMed  Google Scholar 

  36. Guerrero A, Darszon A (1989) Evidence for the activation of two different Ca2+ channels during the egg jelly-induced acrosome reaction of sea urchin sperm. J Biol Chem 264:19593–19599

    CAS  PubMed  Google Scholar 

  37. Beltran C, Darszon A, Labarca P, Lievano A (1994) A high-conductance voltage-dependent multistate Ca2+ channel found in sea urchin and mouse spermatozoa. FEBS Lett 338:23–26

    CAS  PubMed  Google Scholar 

  38. Weyand I, Godde M, Frings S, Weiner J, Muller F, Altenhofen W, Hatt H, Kaupp UB (1994) Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm. Nature 368:859–863

    CAS  PubMed  Google Scholar 

  39. Lievano A, Santi CM, Serrano CJ, Trevino CL, Bellve AR, Hernandez-Cruz A, Darszon A (1996) T-type Ca2+ channels and alpha1E expression in spermatogenic cells, and their possible relevance to the sperm acrosome reaction. FEBS Lett 388:150–154

    CAS  PubMed  Google Scholar 

  40. Goodwin LO, Leeds NB, Hurley I, Mandel FS, Pergolizzi RG, Benoff S (1997) Isolation and characterization of the primary structure of testis-specific L-type calcium channel: implications for contraception. Mol Hum Reprod 3:255–268

    CAS  PubMed  Google Scholar 

  41. O’Toole CM, Arnoult C, Darszon A, Steinhardt RA, Florman HM (2000) Ca(2+) entry through store-operated channels in mouse sperm is initiated by egg ZP3 and drives the acrosome reaction. Mol Biol Cell 11:1571–1584

    PubMed Central  PubMed  Google Scholar 

  42. Lobley A, Pierron V, Reynolds L, Allen L, Michalovich D (2003) Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis. Reprod Biol Endocrinol 1:53

    PubMed Central  PubMed  Google Scholar 

  43. Trevino CL, Felix R, Castellano LE, Gutierrez C, Rodriguez D, Pacheco J, Lopez-Gonzalez I, Gomora JC, Tsutsumi V, Hernandez-Cruz A, Fiordelisio T, Scaling AL, Darszon A (2004) Expression and differential cell distribution of low-threshold Ca(2+) channels in mammalian male germ cells and sperm. FEBS Lett 563:87–92

    CAS  PubMed  Google Scholar 

  44. Delmas P (2004) Assembly and gating of TRPC channels in signalling microdomains. Novartis Found Symp 258:75–89 (discussion 89–102, 263-6.:75–89)

    CAS  PubMed  Google Scholar 

  45. Nilius B (2007) TRP channels in disease. Biochim Biophys Acta 1772:805–812

    CAS  PubMed  Google Scholar 

  46. Voets T, Talavera K, Owsianik G, Nilius B (2005) Sensing with TRP channels. Nat Chem Biol 1:85–92

    CAS  PubMed  Google Scholar 

  47. Trevino CL, Serrano CJ, Beltran C, Felix R, Darszon A (2001) Identification of mouse trp homologs and lipid rafts from spermatogenic cells and sperm. FEBS Lett 509:119–125

    CAS  PubMed  Google Scholar 

  48. Wissenbach U, Schroth G, Philipp S, Flockerzi V (1998) Structure and mRNA expression of a bovine trp homologue related to mammalian trp2 transcripts. FEBS Lett 429:61–66

    CAS  PubMed  Google Scholar 

  49. Castellano LE, Trevino CL, Rodriguez D, Serrano CJ, Pacheco J, Tsutsumi V, Felix R, Darszon A (2003) Transient receptor potential (TRPC) channels in human sperm: expression, cellular localization and involvement in the regulation of flagellar motility. FEBS Lett 541:69–74

    CAS  PubMed  Google Scholar 

  50. Jungnickel MK, Marrero H, Birnbaumer L, Lemos JR, Florman HM (2001) Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nat Cell Biol 3:499–502

    CAS  PubMed  Google Scholar 

  51. Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C (1995) TRPC1, a human homolog of a Drosophila store-operated channel. Proc Natl Acad Sci USA 92:9652–9656

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Sinkins WG, Estacion M, Schilling WP (1998) Functional expression of TrpC1: a human homologue of the Drosophila Trp channel. Biochem J 331:331–339

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Rao JN, Platoshyn O, Golovina VA, Liu L, Zou T, Marasa BS, Turner DJ, Yuan JX, Wang JY (2006) TRPC1 functions as a store-operated Ca2+ channel in intestinal epithelial cells and regulates early mucosal restitution after wounding. Am J Physiol Gastrointest Liver Physiol 290:G782–G792

    CAS  PubMed  Google Scholar 

  54. Xu SZ, Beech DJ (2001) TrpC1 is a membrane-spanning subunit of store-operated Ca(2+) channels in native vascular smooth muscle cells. Circ Res 88:84–87

    CAS  PubMed  Google Scholar 

  55. Antoniotti S, Lovisolo D, Fiorio PA, Munaron L (2002) Expression and functional role of bTRPC1 channels in native endothelial cells. FEBS Lett 510:189–195

    CAS  PubMed  Google Scholar 

  56. Fiorio PA, Maric D, Brazer SC, Giacobini P, Liu X, Chang YH, Ambudkar IS, Barker JL (2005) Canonical transient receptor potential 1 plays a role in basic fibroblast growth factor (bFGF)/FGF receptor-1-induced Ca2+ entry and embryonic rat neural stem cell proliferation. J Neurosci 25:2687–2701

    Google Scholar 

  57. Wu X, Zagranichnaya TK, Gurda GT, Eves EM, Villereal ML (2004) A TRPC1/TRPC3-mediated increase in store-operated calcium entry is required for differentiation of H19-7 hippocampal neuronal cells. J Biol Chem 279:43392–43402

    CAS  PubMed  Google Scholar 

  58. Liu X, Bandyopadhyay BC, Singh BB, Groschner K, Ambudkar IS (2005) Molecular analysis of a store-operated and 2-acetyl-sn-glycerol-sensitive non-selective cation channel. Heteromeric assembly of TRPC1-TRPC3. J Biol Chem 280:21600–21606

    CAS  PubMed  Google Scholar 

  59. Sours-Brothers S, Ding M, Graham S, Ma R (2009) Interaction between TRPC1/TRPC4 assembly and STIM1 contributes to store-operated Ca2+ entry in mesangial cells. Exp Biol Med (Maywood) 234:673–682

    CAS  Google Scholar 

  60. Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655

    CAS  PubMed  Google Scholar 

  61. Bai CX, Giamarchi A, Rodat-Despoix L, Padilla F, Downs T, Tsiokas L, Delmas P (2008) Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits. EMBO Rep 9:472–479

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Zagranichnaya TK, Wu X, Villereal ML (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J Biol Chem 280:29559–29569

    CAS  PubMed  Google Scholar 

  63. Ong HL, Cheng KT, Liu X, Bandyopadhyay BC, Paria BC, Soboloff J, Pani B, Gwack Y, Srikanth S, Singh BB, Gill DL, Ambudkar IS (2007) Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components. J Biol Chem 282:9105–9116

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S (2007) STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol 9: 636–645

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Saleh SN, Albert AP, Large WA (2009) Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP(3) and PIP(2) in rabbit coronary artery myocytes. J Physiol 587:5361–5375

    PubMed Central  CAS  PubMed  Google Scholar 

  66. Maroto R, Raso A, Wood TG, Kurosky A, Martinac B, Hamill OP (2005) TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat Cell Biol 7:179–185

    CAS  PubMed  Google Scholar 

  67. Liu X, Cheng KT, Bandyopadhyay BC, Pani B, Dietrich A, Paria BC, Swaim WD, Beech D, Yildrim E, Singh BB, Birnbaumer L, Ambudkar IS (2007) Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice. Proc Natl Acad Sci USA 104:17542–17547

    PubMed Central  CAS  PubMed  Google Scholar 

  68. Alfonso S, Benito O, Alicia S, Angelica Z, Patricia G, Diana K, Vaca L (2008) Regulation of the cellular localization and function of human transient receptor potential channel 1 by other members of the TRPC family. Cell Calcium 43:375–387

    CAS  PubMed  Google Scholar 

  69. Stamboulian S, Moutin MJ, Treves S, Pochon N, Grunwald D, Zorzato F, De Waard M, Ronjat M, Arnoult C (2005) Junctate, an inositol 1,4,5-triphosphate receptor associated protein, is present in rodent sperm and binds TRPC2 and TRPC5 but not TRPC1 channels. Dev Biol 286:326–337

    CAS  PubMed  Google Scholar 

  70. Vannier B, Peyton M, Boulay G, Brown D, Qin N, Jiang M, Zhu X, Birnbaumer L (1999) Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel. Proc Natl Acad Sci USA 96:2060–2064

    PubMed Central  CAS  PubMed  Google Scholar 

  71. Hofmann T, Schaefer M, Schultz G, Gudermann T (2000) Cloning, expression and subcellular localization of two novel splice variants of mouse transient receptor potential channel 2. Biochem J 351:115–122

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Liman ER, Corey DP, Dulac C (1999) TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc Natl Acad Sci USA 96:5791–5796

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Menco BP, Carr VM, Ezeh PI, Liman ER, Yankova MP (2001) Ultrastructural localization of G-proteins and the channel protein TRP2 to microvilli of rat vomeronasal receptor cells. J Comp Neurol 438:468–489

    CAS  PubMed  Google Scholar 

  74. Brann JH, Dennis JC, Morrison EE, Fadool DA (2002) Type-specific inositol 1,4,5-trisphosphate receptor localization in the vomeronasal organ and its interaction with a transient receptor potential channel, TRPC2. J Neurochem 83:1452–1460

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Chu X, Cheung JY, Barber DL, Birnbaumer L, Rothblum LI, Conrad K, Abrasonis V, Chan YM, Stahl R, Carey DJ, Miller BA (2002) Erythropoietin modulates calcium influx through TRPC2. J Biol Chem 277:34375–34382

    CAS  PubMed  Google Scholar 

  76. Tong Q, Chu X, Cheung JY, Conrad K, Stahl R, Barber DL, Mignery G, Miller BA (2004) Erythropoietin-modulated calcium influx through TRPC2 is mediated by phospholipase Cgamma and IP3R. Am J Physiol Cell Physiol 287:C1667–C1678

    CAS  PubMed  Google Scholar 

  77. Heiner I, Eisfeld J, Halaszovich CR, Wehage E, Jungling E, Zitt C, Luckhoff A (2003) Expression profile of the transient receptor potential (TRP) family in neutrophil granulocytes: evidence for currents through long TRP channel 2 induced by ADP-ribose and NAD. Biochem J 371:1045–1053

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Sutton KA, Jungnickel MK, Wang Y, Cullen K, Lambert S, Florman HM (2004) Enkurin is a novel calmodulin and TRPC channel binding protein in sperm. Dev Biol 274:426–435

    CAS  PubMed  Google Scholar 

  79. Leypold BG, Yu CR, Leinders-Zufall T, Kim MM, Zufall F, Axel R (2002) Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci USA 99:6376–6381

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Stowers L, Holy TE, Meister M, Dulac C, Koentges G (2002) Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science 295:1493–1500

    CAS  PubMed  Google Scholar 

  81. Hurst RS, Zhu X, Boulay G, Birnbaumer L, Stefani E (1998) Ionic currents underlying HTRP3 mediated agonist-dependent Ca2+ influx in stably transfected HEK293 cells. FEBS Lett 422:333–338

    CAS  PubMed  Google Scholar 

  82. Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L (1996) trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell 85:661–671

    CAS  PubMed  Google Scholar 

  83. Dietrich A, Schnitzler M, Emmel J, Kalwa H, Hofmann T, Gudermann T (2003) N-linked protein glycosylation is a major determinant for basal TRPC3 and TRPC6 channel activity. J Biol Chem 278:47842–47852

    CAS  PubMed  Google Scholar 

  84. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–263

    CAS  PubMed  Google Scholar 

  85. Kamouchi M, Philipp S, Flockerzi V, Wissenbach U, Mamin A, Raeymaekers L, Eggermont J, Droogmans G, Nilius B (1999) Properties of heterologously expressed hTRP3 channels in bovine pulmonary artery endothelial cells. J Physiol 518(Pt 2):345–358

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Li HS, Xu XZ, Montell C (1999) Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron 24:261–273

    CAS  PubMed  Google Scholar 

  87. Trebak M, St JB, McKay RR, Birnbaumer L, Putney JW Jr (2003) Signaling mechanism for receptor-activated canonical transient receptor potential 3 (TRPC3) channels. J Biol Chem 278:16244–16252

    CAS  PubMed  Google Scholar 

  88. Trebak M, Hempel N, Wedel BJ, Smyth JT, Bird GS, Putney JW Jr (2005) Negative regulation of TRPC3 channels by protein kinase C-mediated phosphorylation of serine 712. Mol Pharmacol 67:558–563

    CAS  PubMed  Google Scholar 

  89. Thebault S, Zholos A, Enfissi A, Slomianny C, Dewailly E, Roudbaraki M, Parys J, Prevarskaya N (2005) Receptor-operated Ca2+ entry mediated by TRPC3/TRPC6 proteins in rat prostate smooth muscle (PS1) cell line. J Cell Physiol 204:320–328

    CAS  PubMed  Google Scholar 

  90. Vazquez G, Lievremont JP, St JB, Putney JW Jr (2001) Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B lymphocytes. Proc Natl Acad Sci USA 98:11777–11782

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Kiselyov K, Xu X, Mozhayeva G, Kuo T, Pessah I, Mignery G, Zhu X, Birnbaumer L, Muallem S (1998) Functional interaction between InsP3 receptors and store-operated Htrp3 channels. Nature 396:478–482

    CAS  PubMed  Google Scholar 

  92. Wu X, Babnigg G, Villereal ML (2000) Functional significance of human trp1 and trp3 in store-operated Ca(2+) entry in HEK-293 cells. Am J Physiol Cell Physiol 278:C526–C536

    CAS  PubMed  Google Scholar 

  93. Kaznacheyeva E, Glushankova L, Bugaj V, Zimina O, Skopin A, Alexeenko V, Tsiokas L, Bezprozvanny I, Mozhayeva GN (2007) Suppression of TRPC3 leads to disappearance of store-operated channels and formation of a new type of store-independent channels in A431 cells. J Biol Chem 282:23655–23662

    CAS  PubMed  Google Scholar 

  94. Kim MS, Hong JH, Li Q, Shin DM, Abramowitz J, Birnbaumer L, Muallem S (2009) Deletion of TRPC3 in mice reduces store-operated Ca2+ influx and the severity of acute pancreatitis. Gastroenterology 137:1509–1517

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Yildirim E, Kawasaki BT, Birnbaumer L (2005) Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel. Proc Natl Acad Sci USA 102:3307–3311

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Trebak M, Vazquez G, Bird GS, Putney JW Jr (2003) The TRPC3/6/7 subfamily of cation channels. Cell Calcium 33:451–461

    CAS  PubMed  Google Scholar 

  97. Vazquez G, Wedel BJ, Trebak M, St John BG, Putney JW Jr (2003) Expression level of the canonical transient receptor potential 3 (TRPC3) channel determines its mechanism of activation. J Biol Chem 278:21649–21654

    CAS  PubMed  Google Scholar 

  98. Venkatachalam K, Ma HT, Ford DL, Gill DL (2001) Expression of functional receptor-coupled TRPC3 channels in DT40 triple receptor InsP3 knockout cells. J Biol Chem 276:33980–33985

    CAS  PubMed  Google Scholar 

  99. Ohki G, Miyoshi T, Murata M, Ishibashi K, Imai M, Suzuki M (2000) A calcium-activated cation current by an alternatively spliced form of Trp3 in the heart. J Biol Chem 275:39055–39060

    CAS  PubMed  Google Scholar 

  100. Lintschinger B, Balzer-Geldsetzer M, Baskaran T, Graier WF, Romanin C, Zhu MX, Groschner K (2000) Coassembly of Trp1 and Trp3 proteins generates diacylglycerol- and Ca2+-sensitive cation channels. J Biol Chem 275:27799–27805

    CAS  PubMed  Google Scholar 

  101. Poteser M, Graziani A, Rosker C, Eder P, Derler I, Kahr H, Zhu MX, Romanin C, Groschner K (2006) TRPC3 and TRPC4 associate to form a redox-sensitive cation channel. Evidence for expression of native TRPC3-TRPC4 heteromeric channels in endothelial cells. J Biol Chem 281:13588–13595

    CAS  PubMed  Google Scholar 

  102. Groschner K, Rosker C, Lukas M (2004) Role of TRP channels in oxidative stress. Novartis Found Symp 258:222–230 (discussion 231-5, 263-6.:222-230)

    CAS  PubMed  Google Scholar 

  103. Amiri H, Schultz G, Schaefer M (2003) FRET-based analysis of TRPC subunit stoichiometry. Cell Calcium 33:463–470

    CAS  PubMed  Google Scholar 

  104. Rosker C, Graziani A, Lukas M, Eder P, Zhu MX, Romanin C, Groschner K (2004) Ca(2+) signaling by TRPC3 involves Na(+) entry and local coupling to the Na(+)/Ca(2+) exchanger. J Biol Chem 279:13696–13704

    CAS  PubMed  Google Scholar 

  105. Goel M, Zuo CD, Sinkins WG, Schilling WP (2007) TRPC3 channels colocalize with Na+/Ca2+ exchanger and Na+ pump in axial component of transverse-axial tubular system of rat ventricle. Am J Physiol Heart Circ Physiol 292:H874–H883

    CAS  PubMed  Google Scholar 

  106. Eder P, Probst D, Rosker C, Poteser M, Wolinski H, Kohlwein SD, Romanin C, Groschner K (2007) Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex. Cardiovasc Res 73:111–119

    CAS  PubMed  Google Scholar 

  107. Kraft R (2007) The Na+/Ca2+ exchange inhibitor KB-R7943 potently blocks TRPC channels. Biochem Biophys Res Commun 361:230–236

    CAS  PubMed  Google Scholar 

  108. Philipp S, Strauss B, Hirnet D, Wissenbach U, Mery L, Flockerzi V, Hoth M (2003) TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes. J Biol Chem 278:26629–26638

    CAS  PubMed  Google Scholar 

  109. Bandyopadhyay BC, Swaim WD, Liu X, Redman RS, Patterson RL, Ambudkar IS (2005) Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells. Role in apical Ca2+ influx. J Biol Chem 280:12908–12916

    CAS  PubMed  Google Scholar 

  110. Liu CL, Huang Y, Ngai CY, Leung YK, Yao XQ (2006) TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries. Acta Pharmacol Sin 27:981–990

    CAS  PubMed  Google Scholar 

  111. Cheng HW, James AF, Foster RR, Hancox JC, Bates DO (2006) VEGF activates receptor-operated cation channels in human microvascular endothelial cells. Arterioscler Thromb Vasc Biol 26:1768–1776

    CAS  PubMed  Google Scholar 

  112. Kwan HY, Wong CO, Chen ZY, Dominic Chan TW, Huang Y, Yao X (2009) Stimulation of histamine H2 receptors activates TRPC3 channels through both phospholipase C and phospholipase D. Eur J Pharmacol 602:181–187

    CAS  PubMed  Google Scholar 

  113. Glitsch MD (2010) Activation of native TRPC3 cation channels by phospholipase D. FASEB J 24:318–325

    PubMed  Google Scholar 

  114. Zhang Z, Tang J, Tikunova S, Johnson JD, Chen Z, Qin N, Dietrich A, Stefani E, Birnbaumer L, Zhu MX (2001) Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain. Proc Natl Acad Sci USA 98:3168–3173

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Wedel BJ, Vazquez G, McKay RR, St JB, Putney JW Jr (2003) A calmodulin/inositol 1,4,5-trisphosphate (IP3) receptor-binding region targets TRPC3 to the plasma membrane in a calmodulin/IP3 receptor-independent process. J Biol Chem 278:25758–25765

    CAS  PubMed  Google Scholar 

  116. Kim JY, Zeng W, Kiselyov K, Yuan JP, Dehoff MH, Mikoshiba K, Worley PF, Muallem S (2006) Homer 1 mediates store- and inositol 1,4,5-trisphosphate receptor-dependent translocation and retrieval of TRPC3 to the plasma membrane. J Biol Chem 281:32540–32549

    CAS  PubMed  Google Scholar 

  117. Treves S, Franzini-Armstrong C, Moccagatta L, Arnoult C, Grasso C, Schrum A, Ducreux S, Zhu MX, Mikoshiba K, Girard T, Smida-Rezgui S, Ronjat M, Zorzato F (2004) Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion. J Cell Biol 166:537–548

    PubMed Central  CAS  PubMed  Google Scholar 

  118. Woo JS, Hwang JH, Ko JK, Kim dH, Ma J, Lee EH (2009) Glutamate at position 227 of junctophilin-2 is involved in binding to TRPC3. Mol Cell Biochem 328:25–32

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Zeng W, Yuan JP, Kim MS, Choi YJ, Huang GN, Worley PF, Muallem S (2008) STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol Cell 32:439–448

    PubMed Central  CAS  PubMed  Google Scholar 

  120. Liao Y, Erxleben C, Yildirim E, Abramowitz J, Armstrong DL, Birnbaumer L (2007) Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci USA 104:4682–4687

    PubMed Central  CAS  PubMed  Google Scholar 

  121. Bandyopadhyay BC, Ong HL, Lockwich TP, Liu X, Paria BC, Singh BB, Ambudkar IS (2008) TRPC3 controls agonist-stimulated intracellular Ca2+ release by mediating the interaction between inositol 1,4,5-trisphosphate receptor and RACK1. J Biol Chem 283:32821–32830

    PubMed Central  CAS  PubMed  Google Scholar 

  122. Woodard GE, Lopez JJ, Jardin I, Salido GM, Rosado JA (2010) TRPC3 regulates agonist-stimulated Ca2+ mobilization by mediating the interaction between type I inositol 1,4,5-trisphosphate receptor, RACK1 and Orai1. J Biol Chem 285:8045–8053

    Google Scholar 

  123. Kwan HY, Huang Y, Yao X (2004) Regulation of canonical transient receptor potential isoform 3 (TRPC3) channel by protein kinase G. Proc Natl Acad Sci USA 101:2625–2630

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Kwan HY, Huang Y, Yao X (2006) Protein kinase C can inhibit TRPC3 channels indirectly via stimulating protein kinase G. J Cell Physiol 207:315–321

    CAS  PubMed  Google Scholar 

  125. Kawasaki BT, Liao Y, Birnbaumer L (2006) Role of Src in C3 transient receptor potential channel function and evidence for a heterogeneous makeup of receptor- and store-operated Ca2+ entry channels. Proc Natl Acad Sci USA 103:335–340

    PubMed Central  CAS  PubMed  Google Scholar 

  126. Vazquez G, Wedel BJ, Kawasaki BT, Bird GS, Putney JW Jr (2004) Obligatory role of Src kinase in the signaling mechanism for TRPC3 cation channels. J Biol Chem 279:40521–40528

    CAS  PubMed  Google Scholar 

  127. Lockwich T, Singh BB, Liu X, Ambudkar IS (2001) Stabilization of cortical actin induces internalization of transient receptor potential 3 (Trp3)-associated caveolar Ca2+ signaling complex and loss of Ca2+ influx without disruption of Trp3-inositol trisphosphate receptor association. J Biol Chem 276:42401–42408

    CAS  PubMed  Google Scholar 

  128. Singh BB, Lockwich TP, Bandyopadhyay BC, Liu X, Bollimuntha S, Brazer SC, Combs C, Das S, Leenders AG, Sheng ZH, Knepper MA, Ambudkar SV, Ambudkar IS (2004) VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx. Mol Cell 15:635–646

    CAS  PubMed  Google Scholar 

  129. van Rossum DB, Patterson RL, Sharma S, Barrow RK, Kornberg M, Gill DL, Snyder SH (2005) Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 434:99–104

    PubMed  Google Scholar 

  130. Graziani A, Rosker C, Kohlwein SD, Zhu MX, Romanin C, Sattler W, Groschner K, Poteser M (2006) Cellular cholesterol controls TRPC3 function: evidence from a novel dominant-negative knockdown strategy. Biochem J 396:147–155

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Tomita Y, Kaneko S, Funayama M, Kondo H, Satoh M, Akaike A (1998) Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of TRP, expressed in Xenopus oocytes. Neurosci Lett 248:195–198

    CAS  PubMed  Google Scholar 

  132. Philipp S, Trost C, Warnat J, Rautmann J, Himmerkus N, Schroth G, Kretz O, Nastainczyk W, Cavalie A, Hoth M, Flockerzi V (2000) TRP4 (CCE1) protein is part of native calcium release-activated Ca2+-like channels in adrenal cells. J Biol Chem 275:23965–23972

    CAS  PubMed  Google Scholar 

  133. Freichel M, Suh SH, Pfeifer A, Schweig U, Trost C, Weissgerber P, Biel M, Philipp S, Freise D, Droogmans G, Hofmann F, Flockerzi V, Nilius B (2001) Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4–/– mice. Nat Cell Biol 3:121–127

    CAS  PubMed  Google Scholar 

  134. Tiruppathi C, Minshall RD, Paria BC, Vogel SM, Malik AB (2002) Role of Ca2+ signaling in the regulation of endothelial permeability. Vascul Pharmacol 39:173–185

    CAS  PubMed  Google Scholar 

  135. Tu CL, Chang W, Bikle DD (2005) Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. J Invest Dermatol 124:187–197

    CAS  PubMed  Google Scholar 

  136. Yang H, Mergler S, Sun X, Wang Z, Lu L, Bonanno JA, Pleyer U, Reinach PS (2005) TRPC4 knockdown suppresses epidermal growth factor-induced store-operated channel activation and growth in human corneal epithelial cells. J Biol Chem 280:32230–32237

    PubMed Central  CAS  PubMed  Google Scholar 

  137. Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G (2000) Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J Biol Chem 275:17517–17526

    CAS  PubMed  Google Scholar 

  138. Wu X, Babnigg G, Zagranichnaya T, Villereal ML (2002) The role of endogenous human Trp4 in regulating carbachol-induced calcium oscillations in HEK-293 cells. J Biol Chem 277:13597–13608

    CAS  PubMed  Google Scholar 

  139. Obukhov AG, Nowycky MC (2002) TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca(2+) to trigger exocytosis in neuroendocrine cells. J Biol Chem 277:16172–16178

    CAS  PubMed  Google Scholar 

  140. Jeon JP, Lee KP, Park EJ, Sung TS, Kim BJ, Jeon JH, So I (2008) The specific activation of TRPC4 by Gi protein subtype. Biochem Biophys Res Commun 377:538–543

    CAS  PubMed  Google Scholar 

  141. Mery L, Magnino F, Schmidt K, Krause KH, Dufour JF (2001) Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors. FEBS Lett 487:377–383

    CAS  PubMed  Google Scholar 

  142. Wang X, Pluznick JL, Wei P, Padanilam BJ, Sansom SC (2004) TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells. Am J Physiol Cell Physiol 287:C357–C364

    CAS  PubMed  Google Scholar 

  143. Satoh E, Ono K, Xu F, Iijima T (2002) Cloning and functional expression of a novel splice variant of rat TRPC4. Circ J 66:954–958

    CAS  PubMed  Google Scholar 

  144. Tang Y, Tang J, Chen Z, Trost C, Flockerzi V, Li M, Ramesh V, Zhu MX (2000) Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J Biol Chem 275:37559–37564

    CAS  PubMed  Google Scholar 

  145. Tang J, Lin Y, Zhang Z, Tikunova S, Birnbaumer L, Zhu MX (2001) Identification of common binding sites for calmodulin and inositol 1,4,5-trisphosphate receptors on the carboxyl termini of trp channels. J Biol Chem 276:21303–21310

    PubMed Central  CAS  PubMed  Google Scholar 

  146. Boulay G, Zhu X, Peyton M, Jiang M, Hurst R, Stefani E, Birnbaumer L (1997) Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein. J Biol Chem 272:29672–29680

    CAS  PubMed  Google Scholar 

  147. Zhang L, Guo F, Kim JY, Saffen D (2006) Muscarinic acetylcholine receptors activate TRPC6 channels in PC12D cells via Ca2+ store-independent mechanisms. J Biochem 139:459–470

    CAS  PubMed  Google Scholar 

  148. Jung S, Strotmann R, Schultz G, Plant TD (2002) TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells. Am J Physiol Cell Physiol 282:C347–C359

    CAS  PubMed  Google Scholar 

  149. Maruyama Y, Nakanishi Y, Walsh EJ, Wilson DP, Welsh DG, Cole WC (2006) Heteromultimeric TRPC6-TRPC7 channels contribute to arginine vasopressin-induced cation current of A7r5 vascular smooth muscle cells. Circ Res 98:1520–1527

    CAS  PubMed  Google Scholar 

  150. Hassock SR, Zhu MX, Trost C, Flockerzi V, Authi KS (2002) Expression and role of TRPC proteins in human platelets: evidence that TRPC6 forms the store-independent calcium entry channel. Blood 100:2801–2811

    CAS  PubMed  Google Scholar 

  151. Jardin I, Redondo PC, Salido GM, Rosado JA (2008) Phosphatidylinositol 4,5-bisphosphate enhances store-operated calcium entry through hTRPC6 channel in human platelets. Biochim Biophys Acta 1783:84–97

    CAS  PubMed  Google Scholar 

  152. Redondo PC, Jardin I, Lopez JJ, Salido GM, Rosado JA (2008) Intracellular Ca2+ store depletion induces the formation of macromolecular complexes involving hTRPC1, hTRPC6, the type II IP3 receptor and SERCA3 in human platelets. Biochim Biophys Acta 1783: 1163–1176

    CAS  PubMed  Google Scholar 

  153. Carter RN, Tolhurst G, Walmsley G, Vizuete-Forster M, Miller N, Mahaut-Smith MP (2006) Molecular and electrophysiological characterization of transient receptor potential ion channels in the primary murine megakaryocyte. J Physiol 576:151–162

    PubMed Central  CAS  PubMed  Google Scholar 

  154. Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (2004) Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx. J Biol Chem 279:10514–10522

    CAS  PubMed  Google Scholar 

  155. McMeekin SR, Dransfield I, Rossi AG, Haslett C, Walker TR (2006) E-selectin permits communication between PAF receptors and TRPC channels in human neutrophils. Blood 107:4938–4945

    CAS  PubMed  Google Scholar 

  156. Sergeeva OA, Korotkova TM, Scherer A, Brown RE, Haas HL (2003) Co-expression of non-selective cation channels of the transient receptor potential canonical family in central aminergic neurones. J Neurochem 85:1547–1552

    CAS  PubMed  Google Scholar 

  157. Nasman J, Bart G, Larsson K, Louhivuori L, Peltonen H, Akerman KE (2006) The orexin OX1 receptor regulates Ca2+ entry via diacylglycerol-activated channels in differentiated neuroblastoma cells. J Neurosci 26:10658–10666

    CAS  PubMed  Google Scholar 

  158. Albert AP, Large WA (2003) Synergism between inositol phosphates and diacylglycerol on native TRPC6-like channels in rabbit portal vein myocytes. J Physiol 552:789–795

    PubMed Central  CAS  PubMed  Google Scholar 

  159. Corteling RL, Li S, Giddings J, Westwick J, Poll C, Hall IP (2004) Expression of transient receptor potential C6 and related transient receptor potential family members in human airway smooth muscle and lung tissue. Am J Respir Cell Mol Biol 30:145–154

    CAS  PubMed  Google Scholar 

  160. Spassova MA, Hewavitharana T, Xu W, Soboloff J, Gill DL (2006) A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc Natl Acad Sci USA 103:16586–16591

    PubMed Central  CAS  PubMed  Google Scholar 

  161. Goel M, Sinkins W, Keightley A, Kinter M, Schilling WP (2005) Proteomic analysis of TRPC5- and TRPC6-binding partners reveals interaction with the plasmalemmal Na(+)/K(+)-ATPase. Pflugers Arch 451:87–98

    CAS  PubMed  Google Scholar 

  162. Soboloff J, Spassova M, Xu W, He LP, Cuesta N, Gill DL (2005) Role of endogenous TRPC6 channels in Ca2+ signal generation in A7r5 smooth muscle cells. J Biol Chem 280:39786–39794

    CAS  PubMed  Google Scholar 

  163. Lemos VS, Poburko D, Liao CH, Cole WC, van Breemen C (2007) Na+ entry via TRPC6 causes Ca2+ entry via NCX reversal in ATP stimulated smooth muscle cells. Biochem Biophys Res Commun 352:130–134

    CAS  PubMed  Google Scholar 

  164. Kim EY, Alvarez-Baron CP, Dryer SE (2009) Canonical transient receptor potential channel (TRPC)3 and TRPC6 associate with large-conductance Ca2+-activated K+ (BKCa) channels: role in BKCa trafficking to the surface of cultured podocytes. Mol Pharmacol 75:466–477

    PubMed Central  CAS  PubMed  Google Scholar 

  165. Jardin I, Gomez LJ, Salido GM, Rosado JA (2009) Dynamic interaction of hTRPC6 with the Orai1-STIM1 complex or hTRPC3 mediates its role in capacitative or non-capacitative Ca(2+) entry pathways. Biochem J 420:267–276

    CAS  PubMed  Google Scholar 

  166. Basora N, Boulay G, Bilodeau L, Rousseau E, Payet MD (2003) 20-hydroxyeicosatetraenoic acid (20-HETE) activates mouse TRPC6 channels expressed in HEK293 cells. J Biol Chem 278:31709–31716

    CAS  PubMed  Google Scholar 

  167. Boulay G (2002) Ca(2+)-calmodulin regulates receptor-operated Ca(2+) entry activity of TRPC6 in HEK-293 cells. Cell Calcium 32:201–207

    CAS  PubMed  Google Scholar 

  168. Tseng PH, Lin HP, Hu H, Wang C, Zhu MX, Chen CS (2004) The canonical transient receptor potential 6 channel as a putative phosphatidylinositol 3,4,5-trisphosphate-sensitive calcium entry system. Biochemistry 43:11701–11708

    CAS  PubMed  Google Scholar 

  169. Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (2004) Regulation of TRPC6 channel activity by tyrosine phosphorylation. J Biol Chem 279:18887–18894

    CAS  PubMed  Google Scholar 

  170. Foster RR, Zadeh MA, Welsh GI, Satchell SC, Ye Y, Mathieson PW, Bates DO, Saleem MA (2009) Flufenamic acid is a tool for investigating TRPC6-mediated calcium signalling in human conditionally immortalised podocytes and HEK293 cells. Cell Calcium 45:384–390

    CAS  PubMed  Google Scholar 

  171. Liu D, Maier A, Scholze A, Rauch U, Boltzen U, Zhao Z, Zhu Z, Tepel M (2008) High glucose enhances transient receptor potential channel canonical type 6-dependent calcium influx in human platelets via phosphatidylinositol 3-kinase-dependent pathway. Arterioscler Thromb Vasc Biol 28:746–751

    PubMed  Google Scholar 

  172. Cayouette S, Lussier MP, Mathieu EL, Bousquet SM, Boulay G (2004) Exocytotic insertion of TRPC6 channel into the plasma membrane upon Gq protein-coupled receptor activation. J Biol Chem 279:7241–7246

    CAS  PubMed  Google Scholar 

  173. Lussier MP, Lepage PK, Bousquet SM, Boulay G (2008) RNF24, a new TRPC interacting protein, causes the intracellular retention of TRPC. Cell Calcium 43:432–443

    CAS  PubMed  Google Scholar 

  174. Albert AP, Saleh SN, Large WA (2008) Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes. J Physiol 586:3087–3095

    PubMed Central  CAS  PubMed  Google Scholar 

  175. Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R (2008) Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol 586:4209–4223

    PubMed Central  CAS  PubMed  Google Scholar 

  176. Welsh DG, Morielli AD, Nelson MT, Brayden JE (2002) Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90:248–250

    CAS  PubMed  Google Scholar 

  177. Reiser J, Polu KR, Moller CC, Kenlan P, Altintas MM, Wei C, Faul C, Herbert S, Villegas I, Avila-Casado C, McGee M, Sugimoto H, Brown D, Kalluri R, Mundel P, Smith PL, Clapham DE, Pollak MR (2005) TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 37:739–744

    PubMed Central  CAS  PubMed  Google Scholar 

  178. Foller M, Kasinathan RS, Koka S, Lang C, Shumilina E, Birnbaumer L, Lang F, Huber SM (2008) TRPC6 contributes to the Ca(2+) leak of human erythrocytes. Cell Physiol Biochem 21:183–192

    PubMed  Google Scholar 

  179. Damann N, Owsianik G, Li S, Poll C, Nilius B (2009) The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils. Acta Physiol (Oxf) 195:3–11

    CAS  Google Scholar 

  180. Sel S, Rost BR, Yildirim AO, Sel B, Kalwa H, Fehrenbach H, Renz H, Gudermann T, Dietrich A (2008) Loss of classical transient receptor potential 6 channel reduces allergic airway response. Clin Exp Allergy 38:1548–1558

    CAS  PubMed  Google Scholar 

  181. Hamdollah Zadeh MA, Glass CA, Magnussen A, Hancox JC, Bates DO (2008) VEGF-mediated elevated intracellular calcium and angiogenesis in human microvascular endothelial cells in vitro are inhibited by dominant negative TRPC6. Microcirculation 15: 605–614

    CAS  PubMed  Google Scholar 

  182. Muller M, Essin K, Hill K, Beschmann H, Rubant S, Schempp CM, Gollasch M, Boehncke WH, Harteneck C, Muller WE, Leuner K (2008) Specific TRPC6 channel activation, a novel approach to stimulate keratinocyte differentiation. J Biol Chem 283:33942–33954

    PubMed Central  PubMed  Google Scholar 

  183. Cai R, Ding X, Zhou K, Shi Y, Ge R, Ren G, Jin Y, Wang Y (2009) Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells. Int J Cancer 125:2281–2287

    CAS  PubMed  Google Scholar 

  184. Shi Y, Ding X, He ZH, Zhou KC, Wang Q, Wang YZ (2009) Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer. Gut 58:1443–1450

    CAS  PubMed  Google Scholar 

  185. Yue D, Wang Y, Xiao JY, Wang P, Ren CS (2009) Expression of TRPC6 in benign and malignant human prostate tissues. Asian J Androl 11:541–547

    PubMed Central  CAS  PubMed  Google Scholar 

  186. Santin S, Ars E, Rossetti S, Salido E, Silva I, Garcia-Maset R, Gimenez I, Ruiz P, Mendizabal S, Luciano NJ, Pena A, Camacho JA, Fraga G, Cobo MA, Bernis C, Ortiz A, de Pablos AL, Sanchez-Moreno A, Pintos G, Mirapeix E, Fernandez-Llama P, Ballarin J, Torra R, Zamora I, Lopez-Hellin J, Madrid A, Ventura C, Vilalta R, Espinosa L, Garcia C, Melgosa M, Navarro M, Gimenez A, Cots JV, Alexandra S, Caramelo C, Egido J, San Jose MD, de la CF, Sala P, Raspall F, Vila A, Daza AM, Vazquez M, Ecija JL, Espinosa M, Justa ML, Poveda R, Aparicio C, Rosell J, Muley R, Montenegro J, Gonzalez D, Hidalgo E, de Frutos DB, Trillo E, Gracia S, los Rios FJ (2009) TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis. Nephrol Dial Transplant 24:3089–3096

    CAS  PubMed  Google Scholar 

  187. Hu G, Oboukhova EA, Kumar S, Sturek M, Obukhov AG (2009) Canonical transient receptor potential channels expression is elevated in a porcine model of metabolic syndrome. Mol Endocrinol 23:689–699

    PubMed Central  CAS  PubMed  Google Scholar 

  188. Igarashi P, Somlo S (2002) Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 13:2384–2398

    CAS  PubMed  Google Scholar 

  189. Nauli SM, Zhou J (2004) Polycystins and mechanosensation in renal and nodal cilia. Bioessays 26:844–856

    CAS  PubMed  Google Scholar 

  190. Delmas P, Nauli SM, Li X, Coste B, Osorio N, Crest M, Brown DA, Zhou J (2004) Gating of the polycystin ion channel signaling complex in neurons and kidney cells. FASEB J 18: 740–742

    CAS  PubMed  Google Scholar 

  191. Giamarchi A, Padilla F, Coste B, Raoux M, Crest M, Honore E, Delmas P (2006) The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep 7:787–793

    PubMed Central  CAS  PubMed  Google Scholar 

  192. Gao Z, Ruden DM, Lu X (2003) PKD2 cation channel is required for directional sperm movement and male fertility. Curr Biol 13:2175–2178

    CAS  PubMed  Google Scholar 

  193. Watnick TJ, Jin Y, Matunis E, Kernan MJ, Montell C (2003) A flagellar polycystin-2 homolog required for male fertility in Drosophila. Curr Biol 13:2179–2184

    CAS  PubMed  Google Scholar 

  194. Neill AT, Moy GW, Vacquier VD (2004) Polycystin-2 associates with the polycystin-1 homolog, suREJ3, and localizes to the acrosomal region of sea urchin spermatozoa. Mol Reprod Dev 67:472–477

    CAS  PubMed  Google Scholar 

  195. Hughes J, Ward CJ, Aspinwall R, Butler R, Harris PC (1999) Identification of a human homologue of the sea urchin receptor for egg jelly: a polycystic kidney disease-like protein. Hum Mol Genet 8:543–549

    CAS  PubMed  Google Scholar 

  196. Mengerink KJ, Moy GW, Vacquier VD (2002) suREJ3, a polycystin-1 protein, is cleaved at the GPS domain and localizes to the acrosomal region of sea urchin sperm. J Biol Chem 277:943–948

    CAS  PubMed  Google Scholar 

  197. Vora N, Perrone R, Bianchi DW (2008) Reproductive issues for adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis 51:307–318

    PubMed  Google Scholar 

  198. Sutton KA, Jungnickel MK, Florman HM (2008) A polycystin-1 controls postcopulatory reproductive selection in mice. Proc Natl Acad Sci USA 105:8661–8666

    PubMed Central  CAS  PubMed  Google Scholar 

  199. Ahern GP, Brooks IM, Miyares RL, Wang XB (2005) Extracellular cations sensitize and gate capsaicin receptor TRPV1 modulating pain signaling. J Neurosci 25:5109–5116

    CAS  PubMed  Google Scholar 

  200. Cortright DN, Szallasi A (2004) Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur J Biochem 271:1814–1819

    CAS  PubMed  Google Scholar 

  201. Ferrer-Montiel A, Garcia-Martinez C, Morenilla-Palao C, Garcia-Sanz N, Fernandez-Carvajal A, Fernandez-Ballester G, Planells-Cases R (2004) Molecular architecture of the vanilloid receptor. Insights for drug design. Eur J Biochem 271:1820–1826

    CAS  PubMed  Google Scholar 

  202. Neubert JK, Karai L, Jun JH, Kim HS, Olah Z, Iadarola MJ (2003) Peripherally induced resiniferatoxin analgesia. Pain 104:219–228

    CAS  PubMed  Google Scholar 

  203. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543

    CAS  PubMed  Google Scholar 

  204. Dhaka A, Viswanath V, Patapoutian A (2006) Trp ion channels and temperature sensation. Annu Rev Neurosci 29:135–161

    CAS  PubMed  Google Scholar 

  205. Grimaldi P, Orlando P, Di Siena S, Lolicato F, Petrosino S, Bisogno T, Geremia R, De Petrocellis L, Di Marzo V (2009) The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis. Proc Natl Acad Sci USA 106:11131–11136

    PubMed Central  CAS  PubMed  Google Scholar 

  206. Mizrak SC, Dissel-Emiliani FM (2008) Transient receptor potential vanilloid receptor-1 confers heat resistance to male germ cells. Fertil Steril 90:1290–1293

    CAS  PubMed  Google Scholar 

  207. De Petrocellis L, Bisogno T, Maccarrone M, Davis JB, Finazzi-Agro A, Di Marzo V (2001) The activity of anandamide at vanilloid VR1 receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism. J Biol Chem 276:12856–12863

    PubMed  Google Scholar 

  208. Bernabo N, Pistilli MG, Gloria A, Di Pancrazio C, Falasca G, Barboni B, Mattioli M (2008) Factors affecting TRPV1 receptor immunolocalization in boar spermatozoa capacitated in vitro. Vet Res Commun 32(Suppl 1):S103–S105

    PubMed  Google Scholar 

  209. Francavilla F, Battista N, Barbonetti A, Vassallo MR, Rapino C, Antonangelo C, Pasquariello N, Catanzaro G, Barboni B, Maccarrone M (2009) Characterization of the endocannabinoid system in human spermatozoa and involvement of transient receptor potential vanilloid 1 receptor in their fertilizing ability. Endocrinology 150:4692–4700

    CAS  PubMed  Google Scholar 

  210. Maccarrone M, Barboni B, Paradisi A, Bernabo N, Gasperi V, Pistilli MG, Fezza F, Lucidi P, Mattioli M (2005) Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction. J Cell Sci 118:4393–4404

    CAS  PubMed  Google Scholar 

  211. Auzanneau C, Norez C, Antigny F, Thoreau V, Jougla C, Cantereau A, Becq F, Vandebrouck C (2008) Transient receptor potential vanilloid 1 (TRPV1) channels in cultured rat Sertoli cells regulate an acid sensing chloride channel. Biochem Pharmacol 75:476–483

    CAS  PubMed  Google Scholar 

  212. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313

    CAS  PubMed  Google Scholar 

  213. Li S, Wang X, Ye H, Gao W, Pu X, Yang Z (2010) Distribution profiles of transient receptor potential melastatin- and vanilloid-related channels in rat spermatogenic cells and sperm. Mol Biol Rep 37:1287–1293

    CAS  PubMed  Google Scholar 

  214. Montell C (2001) Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci STKE 2001:re1

    Google Scholar 

  215. Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW (1998) Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res 58:1515–1520

    CAS  PubMed  Google Scholar 

  216. Hunter JJ, Shao J, Smutko JS, Dussault BJ, Nagle DL, Woolf EA, Holmgren LM, Moore KJ, Shyjan AW (1998) Chromosomal localization and genomic characterization of the mouse melastatin gene (Mlsn1). Genomics 54:116–123

    CAS  PubMed  Google Scholar 

  217. Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP (2002) TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 109:397–407

    CAS  PubMed  Google Scholar 

  218. Xu XZ, Moebius F, Gill DL, Montell C (2001) Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Proc Natl Acad Sci USA 98:10692–10697

    PubMed Central  CAS  PubMed  Google Scholar 

  219. Deeds J, Cronin F, Duncan LM (2000) Patterns of melastatin mRNA expression in melanocytic tumors. Hum Pathol 31:1346–1356

    CAS  PubMed  Google Scholar 

  220. Runnels LW, Yue L, Clapham DE (2001) TRP-PLIKa bifunctional protein with kinase and ion channel activities. Science 291:1043–1047

    CAS  PubMed  Google Scholar 

  221. Takezawa R, Schmitz C, Demeuse P, Scharenberg AM, Penner R, Fleig A (2004) Receptor-mediated regulation of the TRPM7 channel through its endogenous protein kinase domain. Proc Natl Acad Sci USA 101:6009–6014

    PubMed Central  CAS  PubMed  Google Scholar 

  222. Monteilh-Zoller MK, Hermosura MC, Nadler MJ, Scharenberg AM, Penner R, Fleig A (2003) TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. J Gen Physiol 121:49–60

    PubMed Central  CAS  PubMed  Google Scholar 

  223. McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58

    CAS  PubMed  Google Scholar 

  224. Tsavaler L, Shapero MH, Morkowski S, Laus R (2001) Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61:3760–3769

    CAS  PubMed  Google Scholar 

  225. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430:748–754

    CAS  PubMed  Google Scholar 

  226. Brauchi S, Orio P, Latorre R (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci USA 101:15494–15499

    PubMed Central  CAS  PubMed  Google Scholar 

  227. De Blas GA, Darszon A, Ocampo AY, Serrano CJ, Castellano LE, Hernandez-Gonzalez EO, Chirinos M, Larrea F, Beltran C, Trevino CL (2009) TRPM8, a versatile channel in human sperm. PLoS One 4:e6095

    PubMed Central  PubMed  Google Scholar 

  228. Shoeb M, Laloraya M, Kumar PG (2010) Progesterone-induced reorganisation of NOX-2 components in membrane rafts is critical for sperm functioning in Capra hircus. Andrologia 42:6 (in press)

    Google Scholar 

  229. Harder T, Simons K (1997) Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. Curr Opin Cell Biol 9:534–542

    CAS  PubMed  Google Scholar 

  230. Helms JB, Zurzolo C (2004) Lipids as targeting signals: lipid rafts and intracellular trafficking. Traffic 5:247–254

    CAS  PubMed  Google Scholar 

  231. Ambudkar IS, Brazer SC, Liu X, Lockwich T, Singh B (2004) Plasma membrane localization of TRPC channels: role of caveolar lipid rafts. Novartis Found Symp 258:63–70 (discussion 70-4, 98-102, 263-6.:63-70)

    CAS  PubMed  Google Scholar 

  232. Brazer SC, Singh BB, Liu X, Swaim W, Ambudkar IS (2003) Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. J Biol Chem 278:27208–27215

    PubMed Central  CAS  PubMed  Google Scholar 

  233. Gervasio OL, Whitehead NP, Yeung EW, Phillips WD, Allen DG (2008) TRPC1 binds to caveolin-3 and is regulated by Src kinase – role in Duchenne muscular dystrophy. J Cell Sci 121:2246–2255

    CAS  PubMed  Google Scholar 

  234. Lockwich TP, Liu X, Singh BB, Jadlowiec J, Weiland S, Ambudkar IS (2000) Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. J Biol Chem 275:11934–11942

    CAS  PubMed  Google Scholar 

  235. Sundivakkam PC, Kwiatek AM, Sharma TT, Minshall RD, Malik AB, Tiruppathi C (2009) Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am J Physiol Cell Physiol 296:C403–C413

    PubMed Central  CAS  PubMed  Google Scholar 

  236. Pani B, Ong HL, Brazer SC, Liu X, Rauser K, Singh BB, Ambudkar IS (2009) Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1. Proc Natl Acad Sci USA 106:20087–20092

    PubMed Central  CAS  PubMed  Google Scholar 

  237. Gu Y, Gorelik J, Spohr HA, Shevchuk A, Lab MJ, Harding SE, Vodyanoy I, Klenerman D, Korchev YE (2002) High-resolution scanning patch-clamp: new insights into cell function. FASEB J 16:748–750

    CAS  PubMed  Google Scholar 

  238. Jimenez-Gonzalez MC, Gu Y, Kirkman-Brown J, Barratt CL, Publicover S (2007) Patch-clamp ‘mapping’ of ion channel activity in human sperm reveals regionalisation and co-localisation into mixed clusters. J Cell Physiol 213:801–808

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant Nos. SP/SO/B-47/2000 (Department of Science and Technology, New Delhi) and BT/PR5512/BRB/10/394/2004 (Department of Biotechnology, New Delhi) to PGK. MS received Senior Research Fellowship (3/1/2/13/07-RHN) from Indian Council of Medical Research, New Delhi.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pradeep G. Kumar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Kumar, P.G., Shoeb, M. (2011). The Role of TRP Ion Channels in Testicular Function. In: Islam, M. (eds) Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, vol 704. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0265-3_46

Download citation

Publish with us

Policies and ethics