Abstract
Transient receptor potential (TRP) channels are not well understood in human atrium, and the present study was therefore designed to investigate whether TRPC channels would mediate the nonselective cation current reported previously and are involved in the formation of store-operated Ca2+ entry (SOCE) channels in human atrial myocytes using approaches of whole-cell patch voltage-clamp, RT-PCR, Western blotting, co-immunoprecipitation, and confocal scanning approaches, etc. We found that a nonselective cation current was recorded under K+-free conditions in human atrial myocytes, and the current was inhibited by the TRP channel blocker La3+. Thapsigargin enhanced the current, and its effect was suppressed by La3+ and prevented by pipette inclusion of anti-TRPC1 antibody. Endothlin-1 and angiotensin II enhanced the current that could be inhibited by La3+. Gene and protein expression of TRPC1 channels were abundant in human atria. In addition, mRNA and protein of STIM1 and Orai1, components of SOCE channels, were abundantly expressed in human atria. Co-immunoprecipitation analysis demonstrated an interaction of TRPC1 with STIM1 and/or Orai1. Ca2+ signaling mediated by SOCE channels was detected by a confocal microscopy technique. These results demonstrate the novel evidence that TRPC1 channels not only mediate the nonselective cation current, but also form SOCE channels in human atria as a component. TRPC1 channels can be activated by endothelin-1 or angiotensin II, which may be involved in the atrial electrical remodeling in patients with atrial fibrillation.
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References
Albert AP, Saleh SN, Peppiatt-Wildman CM, Large WA (2007) Multiple activation mechanisms of store-operated TRPC channels in smooth muscle cells. J Physiol 583:25–36
Alexander SP, Mathie A, Peters JA (2007) Guide to receptors and channels (GRAC), 2nd edition (2007 Revision). Br J Pharmacol 150(Suppl 1):S1–168
Alexander SP, Mathie A, Peters JA (2009) Guide to Receptors and Channels (GRAC), 4th edition Br J Pharmacol 158 Suppl 1:S1-254
Bush EW, Hood DB, Papst PJ, Chapo JA, Minobe W, Bristow MR, Olson EN, McKinsey TA (2006) Canonical transient receptor potential channels promote cardiomyocyte hypertrophy through activation of calcineurin signaling. J Biol Chem 281:33487–33496
Byrne M, Kaye DM, Power J (2008) The synergism between atrial fibrillation and heart failure. J Card Fail 14:320–326
Chen JB, Tao R, Sun HY, Tse HF, Lau CP, Li GR (2010) Multiple Ca2+ signaling pathways regulate intracellular Ca2+ activity in human cardiac fibroblasts. J Cell Physiol 223:68–75
Clapham DE (2007) SnapShot: mammalian TRP channels. Cell 129:220
Crumb WJ Jr, Pigott JD, Clarkson CW (1995) Description of a nonselective cation current in human atrium. Circ Res 77:950–956
Du J, Xie J, Zhang Z, Tsujikawa H, Fusco D, Silverman D, Liang B, Yue L (2010) TRPM7-mediated Ca2+ signals confer fibrogenesis in human atrial fibrillation. Circ Res 106:992–1003
Durin O, Pedrinazzi C, Inama G (2010) Focus on renin-angiotensin system modulation and atrial fibrillation control after GISSI AF results. J Cardiovasc Med (Hagerstown) 11:912–918
Eder P, Molkentin JD (2011) TRPC channels as effectors of cardiac hypertrophy. Circ Res 108:265–272
Fauchier L, de Groote P (2011) Atrial fibrillation and renin-angiotensin-aldosterone system: believe it or not. Europace 13:297–298
Guinamard R, Chatelier A, Demion M, Potreau D, Patri S, Rahmati M, Bois P (2004) Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes. J Physiol 558:75–83
Guinamard R, Demion M, Chatelier A, Bois P (2006) Calcium-activated nonselective cation channels in mammalian cardiomyocytes. Trends Cardiovasc Med 16:245–250
Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121
Harada M, Ledoux J, Qi XY, Maguy A, Ordog B, Murohara T, Kamiya K, Kodama I, Schotten U, Van Wagoner D, Dobrev D, Nattel S (2011) TRPC3 channels regulate cardiac fibroblast proliferation by controlling calcium entry. Heart Rhthm 8:S251
Hu R, He ML, Hu H, Yuan BX, Zang WJ, Lau CP, Tse HF, Li GR (2009) Characterization of calcium signaling pathways in human preadipocytes. J Cell Physiol 220:765–770
Huang J, van Breemen C, Kuo KH, Hove-Madsen L, Tibbits GF (2006) Store-operated Ca2+ entry modulates sarcoplasmic reticulum Ca2+ loading in neonatal rabbit cardiac ventricular myocytes. Am J Physiol Cell Physiol 290:C1572–1582
Huang H, Wang W, Liu P, Jiang Y, Zhao Y, Wei H, Niu W (2009) TRPC1 expression and distribution in rat hearts. Eur J Histochem 53:217–223
Ihara M, Noguchi K, Saeki T, Fukuroda T, Tsuchida S, Kimura S, Fukami T, Ishikawa K, Nishikibe M, Yano M (1992) Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci 50:247–255
Inoue R, Jian Z, Kawarabayashi Y (2009) Mechanosensitive TRP channels in cardiovascular pathophysiology. Pharmacol Ther 123:371–385
Ju YK, Chu Y, Chaulet H, Lai D, Gervasio OL, Graham RM, Cannell MB, Allen DG (2007) Store-operated Ca2+ influx and expression of TRPC genes in mouse sinoatrial node. Circ Res 100:1605–1614
Kamkin A, Kiseleva I, Wagner KD, Bohm J, Theres H, Gunther J, Scholz H (2003) Characterization of stretch-activated ion currents in isolated atrial myocytes from human hearts. Pflugers Arch 446:339–346
Kuwahara K, Wang Y, McAnally J, Richardson JA, Bassel-Duby R, Hill JA, Olson EN (2006) TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Invest 116:3114–3126
Levine MJ, Schweitzer P (2010) Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers in atrial fibrillation. Vnitr Lek 56:1138–1141
Li GR, Feng J, Wang Z, Nattel S (1996) Transmembrane chloride currents in human atrial myocytes. Am J Physiol 270:C500–507
Li M, Jiang J, Yue L (2006) Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. J Gen Physiol 127:525–537
Li GR, Sun H, Deng X, Lau CP (2005) Characterization of ionic currents in human mesenchymal stem cells from bone marrow. Stem Cells 23:371–382
Li GR, Sun HY, Zhang XH, Cheng LC, Chiu SW, Tse HF, Lau CP (2009) Omega-3 polyunsaturated fatty acids inhibit transient outward and ultra-rapid delayed rectifier K+ currents and Na+ current in human atrial myocytes. Cardiovasc Res 81:286–293
Li GR, Wang HB, Qin GW, Jin MW, Tang Q, Sun HY, Du XL, Deng XL, Zhang XH, Chen JB, Chen L, Xu XH, Cheng LC, Chiu SW, Tse HF, Vanhoutte PM, Lau CP (2008) Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs. Circulation 117:2449–2457
Miwa S, Kawanabe Y, Okamoto Y, Masaki T (2005) Ca2+ entry channels involved in endothelin-1-induced contractions of vascular smooth muscle cells. J Smooth Muscle Res 41:61–7532
Nakazawa Y, Ashihara T, Tsutamoto T, Ito M, Horie M (2009) Endothelin-1 as a predictor of atrial fibrillation recurrence after pulmonary vein isolation. Hear Rhythm 6:725–730
Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential cation channels in disease. Physiol Rev 87:165–217
Ohba T, Watanabe H, Murakami M, Takahashi Y, Iino K, Kuromitsu S, Mori Y, Ono K, Iijima T, Ito H (2007) Upregulation of TRPC1 in the development of cardiac hypertrophy. J Mol Cell Cardiol 42:498–507
Ong HL, Ambudkar IS (2011) The dynamic complexity of the TRPC1 channelosome. Channels (Austin) 5:424–431
Onohara N, Nishida M, Inoue R, Kobayashi H, Sumimoto H, Sato Y, Mori Y, Nagao T, Kurose H (2006) TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. EMBO J 25:5305–5316
Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of TRP channels. Annu Rev Physiol 68:685–717
Rowell J, Koitabashi N, Kass DA (2010) TRP-ing up heart and vessels: canonical transient receptor potential channels and cardiovascular disease. J Cardiovasc Transl Res 3:516–524
Saleh SN, Albert AP, Large WA (2009) Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP3 and PIP2 in rabbit coronary artery myocytes. J Physiol 587:5361–5375
Saleh SN, Albert AP, Peppiatt CM, Large WA (2006) Angiotensin II activates two cation conductances with distinct TRPC1 and TRPC6 channel properties in rabbit mesenteric artery myocytes. J Physiol 577:479–495
Seth M, Zhang ZS, Mao L, Graham V, Burch J, Stiber J, Tsiokas L, Winn M, Abramowitz J, Rockman HA, Birnbaumer L, Rosenberg P (2009) TRPC1 channels are critical for hypertrophic signaling in the heart. Circ Res 105:1023–1030
Tao R, Sun HY, Lau CP, Tse HF, Lee HC, Li GR (2011) Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells. J Cell Mol Med 15:2684–2696
Voelkers M, Salz M, Herzog N, Frank D, Dolatabadi N, Frey N, Gude N, Friedrich O, Koch WJ, Katus HA, Sussman MA, Most P (2010) Orai1 and Stim1 regulate normal and hypertrophic growth in cardiomyocytes. J Mol Cell Cardiol 48:1329–1334
Watanabe H, Murakami M, Ohba T, Takahashi Y, Ito H (2008) TRP channel and cardiovascular disease. Pharmacol Ther 118:337–351
Wu X, Eder P, Chang B, Molkentin JD (2010) TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci USA 107:7000–7005
Zhang YH, Sun HY, Chen KH, Du XL, Liu B, Cheng LC, Li X, Jin MW, Li GR (2012) Evidence for functional expression of TRPM7 channels in human atrial myocytes. Basic Res Cardiol 107:282
Zhang YH, Wu W, Sun HY, Deng XL, Cheng LC, Li X, Tse HF, Lau CP, Li GR (2012) Modulation of human cardiac transient outward potassium current by EGFR tyrosine kinase and Src-family kinases. Cardiovasc Res 93:424–433
Acknowledgement
This study was supported by a General Research Fund (771712M) from Research Grant Council of Hong Kong, and a grant from Sun Chieh Yeh Heart Foundation of Hong Kong. Zhang YH, Wu HJ, and Che H are supported by a postgraduate scholarship from University of Hong Kong.
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Zhang, YH., Wu, HJ., Che, H. et al. Functional transient receptor potential canonical type 1 channels in human atrial myocytes. Pflugers Arch - Eur J Physiol 465, 1439–1449 (2013). https://doi.org/10.1007/s00424-013-1291-3
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DOI: https://doi.org/10.1007/s00424-013-1291-3