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TRPC channels and diacylglycerol dependent calcium signaling in rat sensory neurons

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Abstract

Transient receptor potential (TRP) channels of the TRPV, TRPA, and TRPM subfamilies play important roles in somatosensation including nociception. While particularly the Thermo TRPs have been extensively investigated in sensory neurons, the relevance of the subclass of “canonical” TRPC channels in primary afferents is yet elusive. In the present study, we investigated the presence and contribution to Ca2+ transients of TRPC channels in dorsal root ganglion neurons. We found that six of the seven known TRPC subtypes were expressed in lumbar DRG, with TRPC1, C3, and C6 being the most abundant. Microfluorimetric calcium measurements showed Ca2+ influx induced by oleylacylglycerol (OAG), an activator of the TRPC3/C6/C7 subgroup. Furthermore, OAG induced rises in [Ca2+]i were inhibited by SKF96365, an inhibitor of receptor and store operated calcium channel. OAG induced calcium transients were also inhibited by blockers of diacylglycerol (DAG) lipase, lipoxygenase or cyclooxygenase and, intriguingly, by inhibitors of the capsaicin receptor TRPV1. Notably, SKF96365 did not affect capsaicin-induced calcium transients. Taken together, our findings suggest that TRPC are functionally expressed in subpopulations of DRG neurons. These channels, along with TRPV1, contribute to calcium homeostasis in rat sensory neurons.

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References

  • Albert D, Buerkert E, Steinhilber D, Werz O (2003) Induction of 5-lipoxygenase activation in polymorphnucelar leukocytes by 1-oleyl-2-acetylglycerol. Biochim Biophys Acta 1631:85–93

    PubMed  CAS  Google Scholar 

  • Ambudkar IS (2006) Ca2+ signaling microdomains: platform for the assembly and regulation of TRPC channels. Trends Pharmacol Sci 27:25–32

    Article  PubMed  CAS  Google Scholar 

  • Appendino G, Daddario N, Minassi A, Moriello AS, De Petrocellis L, Di Marzo V (2005) The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination. J Med Chem 48:4663–4669

    Article  PubMed  CAS  Google Scholar 

  • Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–1282

    Article  PubMed  CAS  Google Scholar 

  • Bezzerides VJ, Ramsey IS, Kotecha S, Greka A, Clapham DE (2004) Rapid vesicular translocation and insertion of TRP channels. Nat Cell Biol 6:709–720

    Article  PubMed  CAS  Google Scholar 

  • Birnbaumer L, Zhu X, Jiang M, Boulay G, Peyton M, Vannier B, Brown D, Platano D, Sadeghi H, Stefani E, Birnbaumer M (1996) On the molecular basis and regulation of cellular capacitive calcium entry: roles for Trp proteins. Proc Nat Acad Sci USA 93:15192–15202

    Article  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Cesare P, Dekker LV, Sardini A, Parker PJ, McNaughton P (1999) Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat. Neuron 23:617–624

    Article  PubMed  CAS  Google Scholar 

  • Chuang HH, Prescott ED, Kong H, Shields S, Jordt S-E, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4, 5)P2-mediated inhibition. Nature 411:957–962

    Article  PubMed  CAS  Google Scholar 

  • Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517–524

    Article  PubMed  CAS  Google Scholar 

  • Clapham DE, Runnels LW, Strübing C (2001) The TRP ion channel family. Nature Reviews Neurosci 2:387–396

    Article  CAS  Google Scholar 

  • Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187

    Article  PubMed  CAS  Google Scholar 

  • Distler C, Rathee PK, Lips KS, Obreja O, Neuhuber W, Kress M (2003) Fast Ca2 + -induced potentiation of heat-activated ionic currents is mediated by cAMP/PKA signalling and requires functional AKAP anchoring. J Neurophysiol 89:2499–2505

    Article  PubMed  CAS  Google Scholar 

  • Dittert I, Vlachová V, Knotková H, Vitaskova Z, Vyklicky L, Kress M, Reeh PW (1998) A technique for fast application of heated solutions of different composition in cultured neurons. J Neurosci Meth 82:195–201

    Article  CAS  Google Scholar 

  • Elg S, Marmigere FC, Mattsson JP, Ernfors P (2007) Cellular subtype distribution and developmental regulation of TRPC channel members in the mouse dorsal root ganglion. J Comp Neurol 503:35–46

    Article  PubMed  CAS  Google Scholar 

  • Erriquez J, Gilardino A, Ariano P, Munaron L, Lovisolo D, Distasi C (2005) Calcium signals activated by arachidonic acid in embryonic chick ciliary ganglion neurons. Neurosignals 14:244–254

    Article  PubMed  CAS  Google Scholar 

  • Estacion M, Li S, Sinkins WG, Gosling M, Bahra P, Poll C, Westwick J, Schilling WP (2006) Activation of human TRPC6 channels by receptor stimulation. J Biol Chem 279:22047–22056

    Article  Google Scholar 

  • Garcia-Martinez C, Fernandez-Carvajal A, Valenzuela B, Gomis A, Van Den Nest W, Ferroni S, Carreno C, Belmonte C, Ferrer-Montiel A (2006) Design and characterization of non-competitive antagonist of the TRPV1 channel with in vivo analgesic and antiinflammatory activity. J Pain 7:735–746

    Article  PubMed  CAS  Google Scholar 

  • Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan VN, Toth A, Pearce LV, Vanderah TW, Porreca F, Blumberg PM, Lile J, Sun Y, Wild K, Louis JC, Treanor JJ (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295

    Article  PubMed  CAS  Google Scholar 

  • Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450

    PubMed  CAS  Google Scholar 

  • Guenther S, Reeh PW, Kress M (1999) Rises in [Ca2+]i mediate capsaicin- and proton-induced heat sensitization of rat primary nociceptive neurons. Eur J NeuroSci 11:3143–3150

    Article  PubMed  CAS  Google Scholar 

  • Haberberger RV, Scholz A, Kummer W, Kress M (2000) M2-receptor subtype does not mediate muscarine-induced increases in [Ca2+]i in nociceptive neurons of rat dorsal root ganglia. J Neurophysiol 84:1934–1941

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Hofmann T, Schaefer M, Schultz G, Gudermann T (2000) Transient receptor potential channels as molecular substrates of receptor-mediated cation entry. J Mol Med 78:14–25

    Article  PubMed  CAS  Google Scholar 

  • Hornig C, Albert D, Fischer L, Hornig M, Radmark O, Steinhilber D, Werz O (2005) 1-Oleyl-2-acetylglycerol stimulates 5-Lipoxygenase activity via a putative (phospho) lipid binding site wihtin the N-terminal C2-like domain. J Biol Chem 280:26913–26921

    Article  PubMed  Google Scholar 

  • Kim JY, Zeng W, Kiselyov K, Yuan JP, Dehof 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

    Article  PubMed  CAS  Google Scholar 

  • Kress M, Guenther S (1999) The role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons. J Neurophysiol 81:2612–2619

    PubMed  CAS  Google Scholar 

  • Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50:277–289

    Article  PubMed  CAS  Google Scholar 

  • Kwon Y, Hofmann T, Montell C (2007) Integration of phosphoinositide- and calmodulin-mediated regulation of TRPC6. Mol Cell 25:491–503

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Linhart O, Obreja O, Kress M (2003) The inflammatory mediators serotonin, prostaglandin E2 and bradykinin evoke calcium influx in rat sensory neurons. Neurosci 118:69–74

    Article  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Ma H-T, Patterson RL, van Rossum DB, Birnbaumer L, Mikoshiba K, Gill DL (2000) Requirement of the inositol triphospate receptor for activation of store-operated Ca2+ channels. Science 287:1647–1651

    Article  PubMed  CAS  Google Scholar 

  • Ma R, Pluznick J, Kudlacek P, Sansom SC (2001) Protein kinase C activates store-operated Ca(2 +) channels in human glomerular mesangial cells. J Biol Chem 276:25759–25765

    Article  PubMed  CAS  Google Scholar 

  • Ma H-T, Venkatachalam K, Parys JB, Gill DL (2002) Modification of store-operated channel coupling and inositol triphosphate receptor function by 2-aminoethoxydiphenyl borate in DT40 lymphocytes. J Biol Chem 277:6915–6922

    Article  PubMed  CAS  Google Scholar 

  • Mehta D, Ahmmed GU, Paria BC, Holinstat M, Voyno-Yasenetskaya D, Tiruppathi C, Minshall RD, Malik AB (2003) RhoA interaction with inositol 1, 4, 5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2 + entry. Role in signaling increased endothelial permeability. J Biol Chem 278:33492–33500

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Michel FJ, Fortin GD, Martel P, Yeomans J, Trudeau LE (2005) M3-like muscarinic receptors mediate Ca2+ influx in rat mesencephalic GABAergic neurones through a protein kinase C-dependent mechanism. Neuropharmacology 48:796–809

    Article  PubMed  CAS  Google Scholar 

  • Mizuno N, Kitayama S, Saishin Y, Shimada S, Morita K, Mitsuhata C, Kurihara H, Dohi T (1999) Molecular cloning and characterization of rat trp homologues from brain. Mol Brain Res 64:41–51

    Article  PubMed  CAS  Google Scholar 

  • Montell C (2005) The TRP superfamily of cation channels. Sci STKE 90:RE1

    Google Scholar 

  • Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Brudford EA, Caterina MJ, Clapham CE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX (2002) A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 9:229–231

    Article  PubMed  CAS  Google Scholar 

  • Morenilla-Palao C, Planells-Cases R, Garcia-Sanz N, Ferrer-Montiel A (2004) Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J Biol Chem 279:25665–25672

    Article  PubMed  CAS  Google Scholar 

  • Mottola A, Antoniotti S, Lovisolo D, Munaron L (2005) Regulation of noncapacitive calcium entry by arachidonic acid and nitric oxide in endothelial cells. FASEB J 19:2075–2077

    PubMed  CAS  Google Scholar 

  • Perney TM, Miller RJ (1989) Two different G-proteins mediate neuropeptide Y and bradykinin-stimulated phospholipid breakdown in cultured rat sensory neurons. J Biol Chem 264:7317–7327

    PubMed  CAS  Google Scholar 

  • Pingle SC, Matta JA, Ahern GP (2007) Capsaicin receptor: TRPV1 a promiscuous TRP channel. Handbook Exp Pharmacol 179:155–171

    Article  CAS  Google Scholar 

  • Rathee PK, Distler C, Obreja O, Neuhuber W, Wang GK, Wang SY, Nau C, Kress M (2002) PKA/AKAP/VR-1 module: a common link of Gs-mediated signaling to thermal hyperalgesia. J Neurosci 22:4740–4745

    PubMed  CAS  Google Scholar 

  • Reiser G, Hamprecht B (1985) Bradykinin causes a transient rise of intracellular Ca2 + -activity in cultured neural cells. Pflüger’s Arch - Eur J Physiol 405:260–264

    Article  CAS  Google Scholar 

  • Schaefer M (2005) Homo- and heteromeric assembly of TRP channel subunits. Pflüger’s Arch - Eur J Physiol 451:35–42

    Article  CAS  Google Scholar 

  • Stefanini M, DeMartino C, Zamboni L (1967) Fixation of ejaculated spermatozoa for electron microscopy. Nature 216:173–174

    Article  PubMed  CAS  Google Scholar 

  • Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Jricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Szabo B, Urbanski MJ, Bisogno T, Di Marzo V, Mediguren A, Baer W, Freiman I (2006) Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol. J Physiol 577:263–280

    Article  PubMed  CAS  Google Scholar 

  • Tata AM, Tripiciano A, Filippini A, Biagioni S, Augusti-Tocco G (2000) Muscarinic receptors modulate intracellular calcium level in chick sensory neurons. Brain Res 866:65–72

    Article  PubMed  CAS  Google Scholar 

  • 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 Phys 204:320–328

    Article  CAS  Google Scholar 

  • Tominaga M, Tominaga T (2005) Structure and function of TRPV1. Pflugers Arch - Eur J Physiol 451:143–150

    Article  CAS  Google Scholar 

  • Tozzi A, Bengtson CP, Longone P, Carignani C, Fusco FR, Bernardi G, Mercuri NB (2003) Involvement of transient receptor potential like channels in responses to mGluRI activation in midbrain dopamine neurons. Eur J NeuroSci 18:2133–2145

    Article  PubMed  Google Scholar 

  • Tsien RY (1981) A non-disruptive technique for loading calcium buffers and indicators into cells. Nature 290:527–528

    Article  PubMed  CAS  Google Scholar 

  • Venkatachalam K, van Rossum DB, Patterson RL, Ma H-T, Gill DL (2002) The cellular and molecular basis of store-operated calcium entry. Nat Cell Biol 4:E263–E272

    Article  PubMed  CAS  Google Scholar 

  • Venkatachalam K, Zheng F, Gill DL (2003) Regulation of canonical transient receptor potential (TRPC) channel function by diacylglycerol and protein kinase C. J Biol Chem 278:29031–29040

    Article  PubMed  CAS  Google Scholar 

  • Wang M, Bianchi R, Chuang SC, Zhao W, Wong RK (2007) Group I metabotropic glutamate receptor-dependent TRPC channel trafficking in hippocampal neurons. J Neurochem 101:411–421

    Article  PubMed  CAS  Google Scholar 

  • Wojcikiewicz RJH (2004) Regulated ubiquitination of proteins in GPCR-initiated signaling pathways. Trends Pharmacol Sci 25:35–41

    Article  PubMed  CAS  Google Scholar 

  • Zeilhofer HU, Reeh PW, Swandulla D, Kress M (1996) Ca2+ permeability of the sustained proton-induced cation current in adult rat dorsal root ganglion neurons. J Neurophysiol 76:2834–2840

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Physiology, DPMP, Innsbruck Medical University, Innsbruck, Austria

    Michaela Kress & Nadja Scherbakov

  2. Institute of Physiology, University Erlangen-Nürnberg, Erlangen-Nürnberg, Germany

    Johannes Karasek

  3. IBMC-UMH, Elche Alicante, Spain

    Antonio V. Ferrer-Montiel

  4. Centre for Neuroscience, Flinders University, Adelaide, Australia

    Rainer Viktor Haberberger

  5. Department of Anatomy and Histology, Mary Overton Neuroscience Research Fellow, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia

    Rainer Viktor Haberberger

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  1. Michaela Kress
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  2. Johannes Karasek
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  3. Antonio V. Ferrer-Montiel
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  4. Nadja Scherbakov
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  5. Rainer Viktor Haberberger
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Correspondence to Rainer Viktor Haberberger.

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Kress, M., Karasek, J., Ferrer-Montiel, A.V. et al. TRPC channels and diacylglycerol dependent calcium signaling in rat sensory neurons. Histochem Cell Biol 130, 655–667 (2008). https://doi.org/10.1007/s00418-008-0477-9

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