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9–Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential

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Abstract

Understanding the role of ionic currents in shaping the cardiac action potential (AP) has great importance as channel malfunctions can lead to sudden cardiac death by inducing arrhythmias. Therefore, researchers frequently use inhibitors to selectively block a certain ion channel like 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC) for calcium-activated chloride current (ICl(Ca)). This study aims to explore which blocker is preferable to study ICl(Ca). Whole-cell voltage-clamp technique was used to record ICa,L, IKs, IKr and IK1, while action potentials were measured using sharp microelectrodes. DIDS- (0.2 mM) and 9-AC-sensitive (0.5 mM) currents were identical in voltage-clamp conditions, regardless of intracellular Ca2+ buffering. DIDS-sensitive current amplitude was larger with the increase of stimulation rate and correlated well with the rate-induced increase of calcium transients. Both drugs increased action potential duration (APD) to the same extent, but the elevation of the plateau potential was more pronounced with 9-AC at fast stimulation rates. On the contrary, 9-AC did not influence either the AP amplitude or the maximal rate of depolarization (V max), but DIDS caused marked reduction of V max. Both inhibitors reduced the magnitude of phase-1, but, at slow stimulation rates, this effect of DIDS was larger. All of these actions on APs were reversible upon washout of the drugs. Increasing concentrations of 9-AC between 0.1 and 0.5 mM in a cumulative manner gradually reduced phase-1 and increased APD. 9-AC at 1 mM had no additional actions upon perfusion after 0.5 mM. The half-effective concentration of 9-AC was approximately 160 μM with a Hill coefficient of 2. The amplitudes of ICa,L, IKs, IKr and IK1 were not changed by 0.5 mM 9-AC. These results suggest that DIDS is equally useful to study ICl(Ca) during voltage-clamp but 9-AC is superior in AP measurements for studying the physiological role of ICl(Ca) due to the lack of sodium channel inhibition. 9-AC has also no action on other ion currents (ICa,L, IKr, IKs, IK1); however, ICa,L tracings can be contaminated with ICl(Ca) when measured in voltage-clamp condition.

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References

  • Bányász T, Horváth B, Virág L, Bárándi L, Szentandrássy N, Harmati G, Magyar J, Marangoni S, Zaza A, Varró A, Nánási PP (2009) Reverse rate dependency is an intrinsic property of canine cardiac preparations. Cardiovasc Res 84:237–244. doi:10.1093/cvr/cvp213, PMID: 19556280

    Article  PubMed  Google Scholar 

  • Baron A, Pacaud P, Loirand G, Mironneau C, Mironneau J (1991) Pharmacological block of Ca(2+)-activated Cl- current in rat vascular smooth muscle cells in short-term primary culture. Pflugers Arch 419:553–558. doi:10.1007/BF00370294, PMID: 1664933

  • Bers DM, Morotti S (2014) Ca(2+) current facilitation is CaMKII-dependent and has arrhythmogenic consequences. Front Pharmacol 5:144. doi:10.3389/fphar.2014.00144, PMID: 24987371

    Article  PubMed Central  PubMed  Google Scholar 

  • Bradley E, Fedigan S, Webb T, Hollywood MA, Thornbury KD, McHale NG, Sergeant GP (2014) Pharmacological characterization of TMEM16A currents. Channels (Austin) 8:308–320. doi:10.4161/chan.28065, PMID: 24642630

    Article  Google Scholar 

  • Busch AE, Busch GL, Ford E et al (1997) The role of the IsK protein in the specific pharmacological properties of the IKs channel complex. Br J Pharmacol 122:187–189. doi:10.1038/sj.bjp.0701434, PMID: 9313924

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cotton KD, Hollywood MA, McHale NG, Thornbury KD (1997) Ca2+ current and Ca(2+)-activated chloride current in isolated smooth muscle cells of the sheep urethra. J Physiol 505:121–131. doi:10.1111/j.1469-7793.1997.121bc.x, PMID: 9409476

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dam VS, Boedtkjer DM, Nyvad J, Aalkjaer C, Matchkov V (2014) TMEM16A knockdown abrogates two different Ca(2+)-activated Cl (−) currents and contractility of smooth muscle in rat mesenteric small arteries. Pflugers Arch 466:1391–1409. doi:10.1007/s00424-013-1382-1, PMID: 24162234

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Duan D (2009) Phenomics of cardiac chloride channels: the systematic study of chloride channel function in the heart. J Physiol 587:2163–2177. doi:10.1113/jphysiol.2008.165860, PMID: 19171656

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eggermont J (2004) Calcium-activated chloride channels: (un)known, (un)loved? Proc Am Thorac Soc 1:22–27. doi:10.1513/pats.2306010, PMID: 16113407

    Article  CAS  PubMed  Google Scholar 

  • Fishman GI, Chugh SS, Dimarco JP et al (2010) Sudden cardiac death prediction and prevention: report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop. Circulation 122:2335–2348. doi:10.1161/CIRCULATIONAHA.110.976092, PMID: 21147730

    Article  PubMed Central  PubMed  Google Scholar 

  • Forrest AS, Joyce TC, Huebner ML et al (2012) Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension. Am J Physiol Cell Physiol 303:C1229–C1243. doi:10.1152/ajpcell.00044.2012, PMID: 23034390

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fülöp L, Fiák E, Szentandrássy N, Magyar J, Nánási PP, Bányász T (2003) The role of transmembrane chloride current in afterdepolarisations in canine ventricular cardiomyocytes. Gen Physiol Biophys 22:341–353, PMID: 14986885

  • Fülöp L, Bányász T, Magyar J, Szentandrássy N, Varró A, Nánási PP (2004) Reopening of L-type calcium channels in human ventricular myocytes during applied epicardial action potentials. Acta Physiol Scand 180:39–47. doi:10.1046/j.0001-6772.2003.01223.x, PMID: 14706111

    Article  PubMed  Google Scholar 

  • Guo D, Young L, Patel C, Jiao Z, Wu Y, Liu T, Kowey PR, Yan GX (2008) Calcium-activated chloride current contributes to action potential alternations in left ventricular hypertrophy rabbit. Am J Physiol Heart Circ Physiol 295:H97–H104. doi:10.1152/ajpheart.01032.2007, PMID: 18441200

    Article  CAS  PubMed  Google Scholar 

  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100. doi:10.1007/BF00656997, PMID: 6270629

    Article  CAS  PubMed  Google Scholar 

  • Harvey RD (1993) Effects of stilbenedisulfonic acid derivatives on the cAMP-regulated chloride current in cardiac myocytes. Pflugers Arch 422:436–442. doi:10.1007/BF00375068, PMID: 8386352

    Article  CAS  PubMed  Google Scholar 

  • Harvey RD, Clark CD, Hume JR (1990) Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential. J Gen Physiol 95:1077–1102. doi:10.1085/jgp.95.6.1077, PMID: 2165130

    Article  CAS  PubMed  Google Scholar 

  • Hirayama Y, Kuruma A, Hiraoka M, Kawano S (2002) Calcium-activated Cl- current is enhanced by acidosis and contributes to the shortening of action potential duration in rabbit ventricular myocytes. Jpn J Physiol 52:293–300. doi:10.2170/jjphysiol.52.293, PMID: 12230806

  • Jones K, Shmygol A, Kupittayanant S, Wray S (2004) Electrophysiological characterization and functional importance of calcium-activated chloride channel in rat uterine myocytes. Pflugers Arch 448:36–43. doi:10.1007/s00424-003-1224-7, PMID: 14740218

    Article  CAS  PubMed  Google Scholar 

  • Kawano S, Hirayama Y, Hiraoka M (1995) Activation mechanism of Ca(2+)-sensitive transient outward current in rabbit ventricular myocytes. J Physiol 486:593–604, PMID: 7473222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Keskanokwong T, Lim HJ, Zhang P, Cheng J, Xu L, Lai D, Wang Y (2011) Dynamic Kv4.3-CaMKII unit in heart: an intrinsic negative regulator for CaMKII activation. Eur Heart J 32:305–315. doi:10.1093/eurheartj/ehq469, PMID: 21148163

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kocic I (2005) Modulators of ion channels activated by hypotonic swelling in cardiomyocytes: new perspectives for pharmacological treatment of life-threatening arrhythmias. Curr Med Chem Cardiovasc Hematol Agents 3:333–339. doi:10.2174/156801605774322274, PMID: 16250864

    Article  CAS  PubMed  Google Scholar 

  • Levesque PC, Clark CD, Zakarov SI, Rosenshtraukh LV, Hume JR (1993) Anion and cation modulation of the guinea-pig ventricular action potential during beta-adrenoceptor stimulation. Pflugers Arch 424:54–62. doi:10.1007/BF00375102, PMID: 8394573

    Article  CAS  PubMed  Google Scholar 

  • Li GR, Du XL, Siow YL, O K, Tse HF, Lau CP (2003) Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential. Cardiovasc Res 58:89–98. doi:10.1016/S0008-6363(02)00859-3, PMID: 12667949

    Article  CAS  PubMed  Google Scholar 

  • Li GR, Sun H, To J, Tse HF, Lau CP (2004) Demonstration of calcium-activated transient outward chloride current and delayed rectifier potassium currents in Swine atrial myocytes. J Mol Cell Cardiol 36:495–504. doi:10.1016/j.yjmcc.2004.01.005, PMID: 15081309

  • Liu J, Lai ZF, Wang XD, Tokutomi N, Nishi K (1998) Inhibition of sodium current by chloride channel blocker 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) in guinea pig cardiac ventricular cells. J Cardiovasc Pharmacol 31:558–567. doi:10.1097/00005344-199804000-00014, PMID: 9554805

    Article  CAS  PubMed  Google Scholar 

  • Oz MC, Sorota S (1995) Forskolin stimulates swelling-induced chloride current, not cardiac cystic fibrosis transmembrane-conductance regulator current, in human cardiac myocytes. Circ Res 76:1063–1070. doi:10.1161/01.RES.76.6.1063, PMID: 7538915

    Article  CAS  PubMed  Google Scholar 

  • Pappone PA, Lee SC (1995) Alpha-adrenergic stimulation activates a calcium-sensitive chloride current in brown fat cells. J Gen Physiol 106:231–258. doi:10.1085/jgp.106.2.231, PMID: 8537817

    Article  CAS  PubMed  Google Scholar 

  • Parameswaran S, Kumar S, Verma RS, Sharma RK (2013) Cardiomyocyte culture - an update on the in vitro cardiovascular model and future challenges. Can J Physiol Pharmacol 91:985–998. doi:10.1139/cjpp-2013-0161, PMID: 24289068

  • Pásek M, Simurda J, Orchard CH (2014) Effect of Ca2+ efflux pathway distribution and exogenous Ca2+ buffers on intracellular Ca2+ dynamics in the rat ventricular myocyte: a simulation study. Biomed Res Int 2014:920208. doi:10.1155/2014/920208, PMID: 24971358

    Article  PubMed Central  PubMed  Google Scholar 

  • Pedemonte N, Galietta LJ (2014) Structure and function of TMEM16 proteins (anoctamins). Physiol Rev 94:419–459. doi:10.1152/physrev.00039.2011, PMID: 24692353

    Article  CAS  PubMed  Google Scholar 

  • Schmitt N, Grunnet M, Olesen SP (2014) Cardiac potassium channel subtypes: new roles in repolarization and arrhythmia. Physiol Rev 94:609–653. doi:10.1152/physrev.00022.2013, PMID: 24692356

    Article  CAS  PubMed  Google Scholar 

  • Shida S, Nakaya H, Kanno M (1992) Effects of Cl- channel blockers on beta-adrenoceptor-mediated decreases in resting potential and intracellular Cl- activity in guinea-pig heart. Eur J Pharmacol 212:267–270. doi:10.1016/0014-2999(92)90341-Z, PMID: 1318214

  • Sipido KR, Callewaert G, Carmeliet E (1993) [Ca2+]i transients and [Ca2+]i-dependent chloride current in single Purkinje cells from rabbit heart. J Physiol 468:641–667, PMID: 8254529

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sipido KR, Volders PG, de Groot SH et al (2000) Enhanced Ca(2+) release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis. Circulation 102:2137–2144. doi:10.1161/01.CIR.102.17.2137, PMID: 11044433

    Article  CAS  PubMed  Google Scholar 

  • Song J, Zhang X, Qi Z et al (2009) Cloning and characterization of a calcium-activated chloride channel in rat uterus. Biol Reprod 80:788–794. doi:10.1095/biolreprod.108.071258, PMID: 19144963

    Article  CAS  PubMed  Google Scholar 

  • Sorota S (1994) Pharmacologic properties of the swelling-induced chloride current of dog atrial myocytes. J Cardiovasc Electrophysiol 5:1006–1016. doi:10.1111/j.1540-8167.1994.tb01143.x, PMID: 7697203

    Article  CAS  PubMed  Google Scholar 

  • Sorota S, Siegal MS, Hoffman BF (1991) The isoproterenol-induced chloride current and cardiac resting potential. J Mol Cell Cardiol 23:1191–1198. doi:10.1016/0022-2828(91)90207-3, PMID: 1749007

    Article  CAS  PubMed  Google Scholar 

  • Strichartz G, Cohen I (1978) Vmax as a measure of GNa in nerve and cardiac membranes. Biophys J 23:153–156. doi:10.1016/S0006-3495(78)85440-X, PMID: 667304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Szabó G, Szentandrássy N, Bíró T, Tóth BI, Czifra G, Magyar J, Bányász T, Varró A, Kovács L, Nánási PP (2005) Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium. Pflugers Arch 450:307–316. doi:10.1007/s00424-005-1445-z, PMID: 15952036

    Article  PubMed  Google Scholar 

  • Szentandrássy N, Nagy D, Ruzsnavszky F et al (2011) Powerful technique to test selectivity of agents acting on cardiac ion channels: the action potential voltage-clamp. Curr Med Chem 18:3737–3756. doi:10.2174/092986711796642418, PMID: 21774754

    Article  PubMed  Google Scholar 

  • Szigeti G, Rusznák Z, Kovács L, Papp Z (1998) Calcium-activated transient membrane currents are carried mainly by chloride ions in isolated atrial, ventricular and Purkinje cells of rabbit heart. Exp Physiol 83:137–153, PMID: 9568474

    Article  CAS  PubMed  Google Scholar 

  • Trafford AW, Díaz ME, Eisner DA (1998) Ca-activated chloride current and Na-Ca exchange have different timecourses during sarcoplasmic reticulum Ca release in ferret ventricular myocytes. Pflugers Arch 435:743–745. doi:10.1007/s004240050577, PMID: 9479029

    Article  CAS  PubMed  Google Scholar 

  • Vandenberg JI, Yoshida A, Kirk K, Powell T (1994) Swelling-activated and isoprenaline-activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology. J Gen Physiol 104:997–1017. doi:10.1085/jgp.104.6.997, PMID: 7699368

    Article  CAS  PubMed  Google Scholar 

  • Verkerk AO, Wilders R, Zegers JG, van Borren MM, Ravesloot JH, Verheijck EE (2002) Ca(2+)-activated Cl(−) current in rabbit sinoatrial node cells. J Physiol 540:105–117. doi:10.1113/jphysiol.2001.013184, PMID: 11927673

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Verkerk AO, Tan HL, Ravesloot JH (2004) Ca2 + −activated Cl- current reduces transmural electrical heterogeneity within the rabbit left ventricle. Acta Physiol Scand 180:239–247. doi:10.1111/j.0001-6772.2003.01252.x, PMID: 14962005

    Article  CAS  PubMed  Google Scholar 

  • Walsh KB, Wang C (1996) Effect of chloride channel blockers on the cardiac CFTR chloride and L-type calcium currents. Cardiovasc Res 32:391–399. doi:10.1016/0008-6363(96)00075-2, PMID: 8796127

    Article  CAS  PubMed  Google Scholar 

  • Wang HS, Dixon JE, McKinnon D (1997) Unexpected and differential effects of Cl- channel blockers on the Kv4.3 and Kv4.2 K+ channels. Implications for the study of the I(to2) current. Circ Res 81:711–718. doi:10.1161/01.RES.81.5.711, PMID: 9351445

  • Wang Z, Feng J, Shi H, Pond A, Nerbonne JM, Nattel S (1999) Potential molecular basis of different physiological properties of the transient outward K+ current in rabbit and human atrial myocytes. Circ Res 84:551–561. doi:10.1161/01.RES.84.5.551, PMID: 10082477

  • Xu Y, Dong PH, Zhang Z, Ahmmed GU, Chiamvimonvat N (2002) Presence of a calcium-activated chloride current in mouse ventricular myocytes. Am J Physiol Heart Circ Physiol 283:H302–H314. doi:10.1152/ajpheart.00044.2002, PMID: 12063303

    CAS  PubMed  Google Scholar 

  • Yang YD, Cho H, Koo JY et al (2008) TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 455:1210–1215. doi:10.1038/nature07313, PMID: 18724360

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Chen Y, An H, Liu H, Li J, Pang C, Ji Q, Zhan Y (2014) A novel biophysical model on calcium and voltage dual dependent gating of calcium-activated chloride channel. J Theor Biol 355:229–235. doi:10.1016/j.jtbi.2014.04.004, PMID: 24727189

    Article  CAS  PubMed  Google Scholar 

  • Zheng XB, Wang R, Yang HL, Sun XL (2013) Effects of chloride ion channel and its blockers on myocardial ischemia reperfusion arrhythmias in rabbits. Zhonghua Yi Xue Za Zhi 93:1168–1173, PMID: 23902890

    CAS  PubMed  Google Scholar 

  • Zhou SS, Gao Z, Dong L, Ding YF, Zhang XD, Wang YM, Pei JM, Gao F, Ma XL (2002) Anion channels influence ECC by modulating L-type Ca(2+) channel in ventricular myocytes. J Appl Physiol 93:1660–1668. doi:10.1152/japplphysiol.00220.2002, PMID: 12381751

    CAS  PubMed  Google Scholar 

  • Zhou SS, Yang J, Li YQ, Zhao LY, Xu M, Ding YF (2005) Effect of Cl- channel blockers on aconitine-induced arrhythmias in rat heart. Exp Physiol 90:865–872. doi:10.1113/expphysiol.2005.031484, PMID: 16118235

    Article  CAS  PubMed  Google Scholar 

  • Zhou SS, Zhang LB, Sun WP, Xiao FC, Zhou YM, Li YJ, Li DL (2007) Effects of monocarboxylic acid-derived Cl- channel blockers on depolarization-activated potassium currents in rat ventricular myocytes. Exp Physiol 92:549–559. doi:10.1113/expphysiol.2007.037069, PMID: 17303647

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt AC (1994) Intracellular calcium activates a chloride current in canine ventricular myocytes. Am J Physiol 267:H1984–H1995, PMID: 7977830

    CAS  PubMed  Google Scholar 

  • Zygmunt AC, Gibbons WR (1991) Calcium-activated chloride current in rabbit ventricular myocytes. Circ Res 68:424–437. doi:10.1161/01.RES.68.2.424, PMID: 1991347

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt AC, Gibbons WR (1992) Properties of the calcium-activated chloride current in heart. J Gen Physiol 99:391–414. doi:10.1085/jgp.99.3.391, PMID: 1375275

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt AC, Robitelle DC, Eddlestone GT (1997) Ito1 dictates behavior of ICl(Ca) during early repolarization of canine ventricle. Am J Physiol 273:H1096–H1106, PMID: 9321794

    CAS  PubMed  Google Scholar 

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Acknowledgments

Financial support was provided by grants from the Hungarian Scientific Research Fund (OTKA-PD101171, OTKA-K100151, OTKA-K101196, OTKA-K109736 and OTKA-NK104331). Further support was obtained from the Hungarian Government (TÁMOP-4.2.2.A-11/1/KONV-2012-0045). This research was realised in the frames of TÁMOP 4.2.4. A/2-11-1-2012-0001 “National Excellence Program–Elaborating and operating an inland student and researcher personal support system convergence program”. The project was subsidised by the European Union and co-financed by the European Social Fund. This paper was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, University of Debrecen, 4012, Debrecen, Nagyerdei krt 98, Hungary

    Krisztina Váczi, Bence Hegyi, Ferenc Ruzsnavszky, Kornél Kistamás, Balázs Horváth, Tamás Bányász, Péter P. Nánási, Norbert Szentandrássy & János Magyar

  2. Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary

    Balázs Horváth

  3. Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary

    Péter P. Nánási & Norbert Szentandrássy

  4. Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    János Magyar

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  1. Krisztina Váczi
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Correspondence to Norbert Szentandrássy.

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Váczi, K., Hegyi, B., Ruzsnavszky, F. et al. 9–Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential. Naunyn-Schmiedeberg's Arch Pharmacol 388, 87–100 (2015). https://doi.org/10.1007/s00210-014-1050-9

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