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Potassium Channels in the Heart

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Channelopathies in Heart Disease

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 6))

Abstract

Ionic currents over the plasma membrane through channels are the cornerstone of excitable cells. Human cardiomyocytes are excitable and continuously cycle between a depolarized and a repolarized state every second throughout human life, initiating and coordinating cardiac pump function. Ion channels selective for potassium (K+) critically participate in cellular repolarization and contribute to stabilizing the diastolic membrane potential, thus shaping the cardiac action potential. Four different subfamilies of potassium channels are present in the heart: small conductance, calcium-activated potassium channels (SK or KCa2), inwardly rectifying potassium channels (Kir), two-pore-domain potassium channels (K2P), and voltage-gated potassium channels (KV). In the present review, the structure and biophysical function of these cardiac potassium ion channels are reviewed. Moreover, rectification, inactivation, and current dependency on the extracellular potassium concentration are explained.

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References

  • An WF, Bowlby MR, Betty M, et al. Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000;403:553–6.

    Article  CAS  PubMed  Google Scholar 

  • Anumonwo JM, Lopatin AN. Cardiac strong inward rectifier potassium channels. J Mol Cell Cardiol. 2010;48:45–54.

    Article  CAS  PubMed  Google Scholar 

  • Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey GK. (V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature. 1996;384:78–80.

    Article  CAS  PubMed  Google Scholar 

  • Berkefeld H, Fakler B, Schulte U. Ca2+−activated K+ channels: from protein complexes to function. Physiol Rev. 2010;90:1437–59.

    Article  CAS  PubMed  Google Scholar 

  • Bertaso F, Sharpe CC, Hendry BM, James AF. Expression of voltage-gated K+ channels in human atrium. Basic Res Cardiol. 2002;97:424–33.

    Article  CAS  PubMed  Google Scholar 

  • Bonilla IM, Long VP 3rd, Vargas-Pinto P, et al. Calcium-activated potassium current modulates ventricular repolarization in chronic heart failure. PLoS One. 2014;9:e108824.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bouchard R, Fedida D. Closed- and open-state binding of 4-aminopyridine to the cloned human potassium channel Kv1.5. J Pharmacol Exp Ther. 1995;275:864–76.

    CAS  PubMed  Google Scholar 

  • Brouillette J, Clark RB, Giles WR, Fiset C. Functional properties of K+ currents in adult mouse ventricular myocytes. J Physiol. 2004;559:777–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brunet S, Aimond F, Li H, et al. Heterogeneous expression of repolarizing, voltage-gated K+ currents in adult mouse ventricles. J Physiol. 2004;559:103–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calloe K, Nof E, Jespersen T, et al. Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes. J Cardiovasc Electrophysiol. 2011;22:1057–66.

    Article  PubMed  PubMed Central  Google Scholar 

  • Calloe K, Goodrow R, Olesen SP, Antzelevitch C, Cordeiro JM. Tissue-specific effects of acetylcholine in the canine heart. Am J Phys Heart Circ Phys. 2013;305:H66–75.

    CAS  Google Scholar 

  • Carrion AM, Link WA, Ledo F, Mellstrom B, Naranjo JR. DREAM is a Ca2+−regulated transcriptional repressor. Nature. 1999;398:80–4.

    Article  CAS  PubMed  Google Scholar 

  • Chang PC, Turker I, Lopshire JC, et al. Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles. J Am Heart Assoc. 2013;2:e004713.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen YH, Xu SJ, Bendahhou S, et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science (New York, NY). 2003;299:251–4.

    Article  CAS  Google Scholar 

  • Cordeiro JM, Calloe K, Aschar-Sobbi R, et al. Physiological roles of the transient outward current Ito in normal and diseased hearts. Front Biosci (Schol Ed). 2016;8:143–59.

    Article  Google Scholar 

  • Decher N, Wemhoner K, Rinne S, et al. Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex. Cell Physiol Biochem. 2011;28:77–86. 19

    Article  CAS  PubMed  Google Scholar 

  • Decher N, Kiper AK, Rolfes C, Schulze-Bahr E, Rinne S. The role of acid-sensitive two-pore domain potassium channels in cardiac electrophysiology: focus on arrhythmias. Pflugers Arch. 2015;467:1055–67.

    Article  CAS  PubMed  Google Scholar 

  • Dong DL, Bai YL, Cai BZ. Calcium-activated potassium channels: potential target for cardiovascular diseases. Adv Protein Chem Struct Biol. 2016;104:233–61.

    Article  CAS  PubMed  Google Scholar 

  • Donner BC, Schullenberg M, Geduldig N, et al. Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability. Basic Res Cardiol. 2011;106:75–87.

    Article  CAS  PubMed  Google Scholar 

  • Ellinghaus P, Scheubel RJ, Dobrev D, et al. Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays. J Thorac Cardiovasc Surg. 2005;129:1383–90.

    Article  CAS  PubMed  Google Scholar 

  • Fakler B, Brandle U, Glowatzki E, Weidemann S, Zenner HP, Ruppersberg JP. Strong voltage-dependent inward rectification of inward rectifier K+ channels is caused by intracellular spermine. Cell. 1995;80:149–54.

    Article  CAS  PubMed  Google Scholar 

  • Feng J, Wible B, Li GR, Wang Z, Nattel S. Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ Res. 1997;80:572–9.

    Article  CAS  PubMed  Google Scholar 

  • Firek L, Giles WR. Outward currents underlying repolarization in human atrial myocytes. Cardiovasc Res. 1995;30:31–8.

    Article  CAS  PubMed  Google Scholar 

  • Fiset C, Clark RB, Shimoni Y, Giles WR. Shal-type channels contribute to the Ca2+-independent transient outward K+ current in rat ventricle. J Physiol. 1997;500(Pt 1):51–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foeger NC, Wang W, Mellor RL, Nerbonne JM. Stabilization of Kv4 protein by the accessory K(+) channel interacting protein 2 (KChIP2) subunit is required for the generation of native myocardial fast transient outward K(+) currents. J Physiol. 2013;591:4149–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freites JA, Schow EV, White SH, Tobias DJ. Microscopic origin of gating current fluctuations in a potassium channel voltage sensor. Biophys J. 2012;102:L44–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaborit N, Le Bouter S, Szuts V, et al. Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart. J Physiol. 2007;582:675–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaborit N, Varro A, Le Bouter S, et al. Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts. J Mol Cell Cardiol. 2010;49:639–46.

    Article  CAS  PubMed  Google Scholar 

  • Gintant GA. Characterization and functional consequences of delayed rectifier current transient in ventricular repolarization. Am J Phys Heart Circ Phys. 2000;278:H806–17.

    CAS  Google Scholar 

  • Giudicessi JR, Ye D, Tester DJ, et al. Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm. 2011;8:1024–32.

    Article  PubMed  PubMed Central  Google Scholar 

  • Goldstein SAN, Bockenhauer D, O’Kelly I, Zilberberg N. Potassium leak channels and the KCNK family of two-p-domain subunits. Nat Rev Neurosci. 2001;2:175–84.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S. International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels. Pharmacol Rev. 2005;57:527–40.

    Article  CAS  PubMed  Google Scholar 

  • Grubb S, Calloe K, Thomsen MB. Impact of KChIP2 on cardiac electrophysiology and the progression of heart failure. Front Physiol. 2012;3:118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grubb S, Speerschneider T, Occhipinti D, et al. Loss of K+ currents in heart failure is accentuated in KChIP2 deficient mice. J Cardiovasc Electrophysiol. 2014;25:896–904.

    Article  PubMed  Google Scholar 

  • Grubb S, Aistrup GL, Koivumaki JT, et al. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2. Am J Phys Heart Circ Phys. 2015;309:H481–9.

    CAS  Google Scholar 

  • Grunnet M, Jespersen T, Angelo K, et al. Pharmacological modulation of SK3 channels. Neuropharmacology. 2001;40:879–87.

    Article  CAS  PubMed  Google Scholar 

  • Guo W, Xu H, London B, Nerbonne JM. Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes. J Physiol. 1999;521(Pt 3):587–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo W, Li H, London B, Nerbonne JM. Functional consequences of elimination of i(to,f) and i(to,s): early afterdepolarizations, atrioventricular block, and ventricular arrhythmias in mice lacking Kv1.4 and expressing a dominant-negative Kv4 alpha subunit. Circ Res. 2000;87:73–9.

    Article  CAS  PubMed  Google Scholar 

  • Guo W, Malin SA, Johns DC, Jeromin A, Nerbonne JM. Modulation of Kv4-encoded K(+) currents in the mammalian myocardium by neuronal calcium sensor-1. J Biol Chem. 2002;277:26436–43.

    Article  CAS  PubMed  Google Scholar 

  • Gutman GA, Chandy KG, Grissmer S, et al. International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev. 2005;57:473–508.

    Article  CAS  PubMed  Google Scholar 

  • Heurteaux C, Guy N, Laigle C, et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J. 2004;23:2684–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev. 2010;90:291–366.

    Article  CAS  PubMed  Google Scholar 

  • Ishibashi K, Suzuki M, Imai M. Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels. Biochem Biophys Res Commun. 2000;270:370–6.

    Article  CAS  PubMed  Google Scholar 

  • Jost N, Virag L, Bitay M, et al. Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle. Circulation. 2005;112:1392–9.

    Article  PubMed  Google Scholar 

  • Kober L, Bloch Thomsen PE, Moller M, et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet (London, England). 2000;356:2052–8.

    Article  CAS  Google Scholar 

  • Koumi S, Wasserstrom JA, Ten Eick RE. Beta-adrenergic and cholinergic modulation of inward rectifier K+ channel function and phosphorylation in Guinea-pig ventricle. J Physiol. 1995a;486(Pt 3):661–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koumi S, Backer CL, Arentzen CE, Sato R. Beta-adrenergic modulation of the inwardly rectifying potassium channel in isolated human ventricular myocytes. Alteration in channel response to beta-18 adrenergic stimulation in failing human hearts. J Clin Invest. 1995b;96:2870–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubo Y, Baldwin TJ, Jan YN, Jan LY. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature. 1993;362:127–33.

    Article  CAS  PubMed  Google Scholar 

  • Kubo Y, Adelman JP, Clapham DE, et al. International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels. Pharmacol Rev. 2005;57:509–26.

    Article  CAS  PubMed  Google Scholar 

  • Kuo HC, Cheng CF, Clark RB, et al. A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia. Cell. 2001;107:801–13.

    Article  CAS  PubMed  Google Scholar 

  • Kurata HT, Fedida D. A structural interpretation of voltage-gated potassium channel inactivation. Prog Biophys Mol Biol. 2006;92:185–208.

    Article  CAS  PubMed  Google Scholar 

  • Li N, Timofeyev V, Tuteja D, et al. Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation. J Physiol. 2009;587:1087–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liin SI, Barro-Soria R, Larsson HP. The KCNQ1 channel—remarkable flexibility in gating allows for functional versatility. J Physiol. 2015;593:2605–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Kim KH, Morales MJ, Heximer SP, Hui CC, Backx PH. Kv4.3-encoded fast transient outward current is presented in Kv4.2 knockout mouse Cardiomyocytes. PLoS One. 2015;10:e0133274.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE. The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature. 1987;325:321–6.

    Article  CAS  PubMed  Google Scholar 

  • London B, Wang DW, Hill JA, Bennett PB. The transient outward current in mice lacking the potassium channel gene Kv1.4. J Physiol. 1998;509(Pt 1):171–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopes CM, Gallagher PG, Buck ME, Butler MH, Goldstein SA. Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J Biol Chem. 2000;275:16969–78.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Barneo J, Hoshi T, Heinemann SH, Aldrich RW. Effects of external cations and mutations in the pore region on C-type inactivation of shaker potassium channels. Recept Channels. 1993;1:61–71.

    CAS  PubMed  Google Scholar 

  • Lu L, Zhang Q, Timofeyev V, et al. Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Circ Res. 2007;100:112–20.

    Article  CAS  PubMed  Google Scholar 

  • Lugenbiel P, Wenz F, Syren P, et al. TREK-1 (K2P2.1) K+ channels are suppressed in patients with atrial fibrillation and heart failure and provide therapeutic targets for rhythm control. Basic Res Cardiol. 2017;112:8.

    Article  PubMed  CAS  Google Scholar 

  • Lundby A, Jespersen T, Schmitt N, et al. Effect of the Ito activator NS5806 on cloned Kv4 channels depends on the accessory protein KChIP2. Br J Pharmacol. 2010;160:2028–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lundby A, Andersen MN, Steffensen AB, et al. In vivo phosphoproteomics analysis reveals the cardiac targets of beta-adrenergic receptor signaling. Sci Signal. 2013;6:rs11.

    Article  PubMed  CAS  Google Scholar 

  • Melnyk P, Zhang L, Shrier A, Nattel S. Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle. Am J Phys Heart Circ Phys. 2002;283:H1123–33.

    CAS  Google Scholar 

  • Mitcheson JS, Sanguinetti MC. Biophysical properties and molecular basis of cardiac rapid and slow delayed rectifier potassium channels. Cell Physiol Biochem. 1999;9:201–16.

    Article  CAS  PubMed  Google Scholar 

  • Morales MJ, Wee JO, Wang S, Strauss HC, Rasmusson RL. The N-terminal domain of a K+ channel beta subunit increases the rate of C-type inactivation from the cytoplasmic side of the channel. Proc Natl Acad Sci U S A. 1996;93:15119–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nabauer M, Beuckelmann DJ, Uberfuhr P, Steinbeck G. Regional differences in current density and rate-dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle. Circulation. 1996;93:168–77.

    Article  CAS  PubMed  Google Scholar 

  • Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev. 2005;85:1205–53.

    Article  CAS  PubMed  Google Scholar 

  • Nichols CG, Makhina EN, Pearson WL, Sha Q, Lopatin AN. Inward rectification and implications for cardiac excitability. Circ Res. 1996;78:1–7.

    Article  CAS  PubMed  Google Scholar 

  • Niwa N, Nerbonne JM. Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation. J Mol Cell Cardiol. 2010;48:12–25.

    Article  CAS  PubMed  Google Scholar 

  • Olesen MS, Refsgaard L, Holst AG, et al. A novel KCND3 gain-of-function mutation associated with early-onset of persistent lone atrial fibrillation. Cardiovasc Res. 2013;98:488–95.

    Article  CAS  PubMed  Google Scholar 

  • Olson TM, Alekseev AE, Liu XK, et al. Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Human molecular genetics 2006;15:2185–91.

    Article  CAS  PubMed  Google Scholar 

  • Oosterhoff P, Thomsen MB, Maas JN, et al. High-rate pacing reduces variability of repolarization and prevents repolarization-dependent arrhythmias in dogs with chronic AV block. J Cardiovasc Electrophysiol. 2010;1384-91(23):21.

    Google Scholar 

  • Ozgen N, Dun W, Sosunov EA, et al. Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites. Cardiovasc Res. 2007;75:758–69.

    Article  CAS  PubMed  Google Scholar 

  • Patel SP, Campbell DL. Transient outward potassium current, ‘Ito’, phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms. J Physiol. 2005;569:7–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perry MD, Ng CA, Mann SA, et al. Getting to the heart of hERG K(+) channel gating. J Physiol. 2015;593:2575–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plaster NM, Tawil R, Tristani-Firouzi M, et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen’s syndrome. Cell. 2001;105:511–9.

    Article  CAS  PubMed  Google Scholar 

  • Pongs O, Schwarz JR. Ancillary subunits associated with voltage-dependent K+ channels. Physiol Rev. 2010;90:755–96.

    Article  CAS  PubMed  Google Scholar 

  • Priori SG, Pandit SV, Rivolta I, et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res. 2005;96(7):800.

    Article  CAS  PubMed  Google Scholar 

  • Radicke S, Cotella D, Graf EM, Ravens U, Wettwer E. Expression and function of dipeptidyl-aminopeptidase-like protein 6 as a putative beta-subunit of human cardiac transient outward current encoded by Kv4.3. J Physiol. 2005;565:751–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rasmusson RL, Morales MJ, Wang S, et al. Inactivation of voltage-gated cardiac K+ channels. Circ Res. 1998;82:739–50.

    Article  CAS  PubMed  Google Scholar 

  • Ravens U, Odening KE. Atrial fibrillation: therapeutic potential of atrial K+ channel blockers. Pharmacol Ther. 2017;176:13–21.

    Article  CAS  PubMed  Google Scholar 

  • Ravens U, Wettwer E. Ultra-rapid delayed rectifier channels: molecular basis and therapeutic implications. Cardiovasc Res. 2011;89:776–85.

    Article  CAS  PubMed  Google Scholar 

  • Rinne S, Kiper AK, Schlichthorl G, et al. TASK-1 and TASK-3 may form heterodimers in human atrial cardiomyocytes. J Mol Cell Cardiol. 2015;81:71–80.

    Article  CAS  PubMed  Google Scholar 

  • Ronkainen JJ, Hanninen SL, Korhonen T, et al. Ca2+-calmodulin-dependent protein kinase II represses cardiac transcription of the L-type calcium channel alpha(1C)-subunit gene (Cacna1c) by DREAM translocation. J Physiol. 2011;2669-86(21):589.

    Google Scholar 

  • Rosati B, Pan Z, Lypen S, et al. Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle. J Physiol. 2001;533:119–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosati B, Grau F, Rodriguez S, Li H, Nerbonne JM, McKinnon D. Concordant expression of KChIP2 mRNA, protein and transient outward current throughout the canine ventricle. J Physiol. 2003;548:815–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sah R, Ramirez RJ, Oudit GY, et al. Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)). J Physiol. 2003;546:5–18.

    Article  CAS  PubMed  Google Scholar 

  • Sakmann B, Noma A, Trautwein W. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature. 1983;303:250–3.

    Article  CAS  PubMed  Google Scholar 

  • Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990;96:195–215.

    Article  CAS  PubMed  Google Scholar 

  • Sanguinetti MC, Jurkiewicz NK. Role of external Ca2+ and K+ in gating of cardiac delayed rectifier K+ currents. Pflugers Arch. 1992;420:180–6.

    Article  CAS  PubMed  Google Scholar 

  • Sanguinetti MC, Curran ME, Zou A, et al. Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature. 1996;384:80–3.

    Article  CAS  PubMed  Google Scholar 

  • Sanguinetti MC, Johnson JH, Hammerland LG, et al. Heteropodatoxins: peptides isolated from spider venom that block Kv4.2 potassium channels. Mol Pharmacol. 1997;51:491–8.

    CAS  PubMed  Google Scholar 

  • Schmidt C, Wiedmann F, Schweizer PA, Katus HA, Thomas D. Inhibition of cardiac two-pore-domain K+ (K2P) channels—an emerging antiarrhythmic concept. Eur J Pharmacol. 2014;738:250–5.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt C, Wiedmann F, Voigt N, et al. Upregulation of K(2P)3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation. Circulation. 2015;132:82–92.

    Article  CAS  PubMed  Google Scholar 

  • Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. 2001;103:89–95.

    Article  CAS  PubMed  Google Scholar 

  • Seebohm G, Sanguinetti MC, Pusch M. Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels. J Physiol. 2003;552:369–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skibsbye L, Poulet C, Diness JG, et al. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria. Cardiovasc Res. 2014;103:156–67.

    Article  CAS  PubMed  Google Scholar 

  • Snyders DJ. Structure and function of cardiac potassium channels. Cardiovasc Res. 1999;42:377–90.

    Article  CAS  PubMed  Google Scholar 

  • Snyders DJ, Tamkun MM, Bennett PB. A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J Gen Physiol. 1993;101:513–43.

    Article  CAS  PubMed  Google Scholar 

  • Soltysinska E, Olesen SP, Christ T, et al. Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts. Pflugers Arch. 2009;459:11–23.

    Article  CAS  PubMed  Google Scholar 

  • Soltysinska E, Bentzen BH, Barthmes M, et al. KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. PLoS One. 2014;9:e103402.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Spector PS, Curran ME, Zou A, Keating MT, Sanguinetti MC. Fast inactivation causes rectification of the IKr channel. J Gen Physiol. 1996;107:611–9.

    Article  CAS  PubMed  Google Scholar 

  • Speerschneider T, Thomsen MB. Physiology and analysis of the electrocardiographic T wave in mice. Acta Physiol (Oxf). 2013;209:262–71.

    Article  CAS  Google Scholar 

  • Speerschneider T, Grubb S, Metoska A, Olesen SP, Calloe K, Thomsen MB. Development of heart failure is independent of K+ channel-interacting protein 2 expression. J Physiol. 2013;591:5923–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Speerschneider T, Grubb S, Olesen SP, Calloe K, Thomsen MB. Ventricular repolarization time, location of pacing stimulus and current pulse amplitude conspire to determine arrhythmogenicity in mice. Acta Physiol (Oxf). 2017;219:660–8.

    Article  CAS  Google Scholar 

  • Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet. 1997;17:338–40.

    Article  CAS  PubMed  Google Scholar 

  • Splawski I, Shen J, Timothy KW, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000;102:1178–85.

    Article  CAS  PubMed  Google Scholar 

  • Tamargo J, Caballero R, Gómez R, Valenzuela C, Delpón E. Pharmacology of cardiac potassium channels. Cardiovasc Res. 2004;62:9–33.

    Article  CAS  PubMed  Google Scholar 

  • Teutsch C, Kondo RP, Dederko DA, Chrast J, Chien KR, Giles WR. Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection. Cardiovasc Res. 2007;73:739–49.

    Article  CAS  PubMed  Google Scholar 

  • Thomsen MB, Verduyn SC, Stengl M, et al. Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs. Circulation. 2004;110:2453–9.

    Article  PubMed  Google Scholar 

  • Thomsen MB, Matz J, Volders PG, Vos MA. Assessing the proarrhythmic potential of drugs: current status of models and surrogate parameters of torsades de pointes arrhythmias. Pharmacol Ther. 2006a;112:150–70.

    Article  CAS  PubMed  Google Scholar 

  • Thomsen MB, Beekman JD, Attevelt NJ, et al. No proarrhythmic properties of the antibiotics Moxifloxacin or azithromycin in anaesthetized dogs with chronic-AV block. Br J Pharmacol. 2006b;149:1039–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomsen MB, Sosunov EA, Anyukhovsky EP, Ozgen N, Boyden PA, Rosen MR. Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration. Heart Rhythm. 2009a;6:370–7.

    Article  PubMed  Google Scholar 

  • Thomsen MB, Wang C, Ozgen N, Wang HG, Rosen MR, Pitt GS. Accessory subunit KChIP2 modulates the cardiac L-type calcium current. Circ Res. 2009b;104:1382–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomsen MB, Foster E, Nguyen KH, Sosunov EA. Transcriptional and electrophysiological consequences of KChIP2-mediated regulation of CaV1.2. Channels (Austin). 2009c;3:308–10.

    Article  CAS  Google Scholar 

  • Tuteja D, Xu D, Timofeyev V, et al. Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Am J Phys Heart Circ Phys. 2005;289:H2714–23.

    CAS  Google Scholar 

  • Unudurthi SD, Wu X, Qian L, et al. Two-pore K+ channel TREK-1 regulates Sinoatrial node membrane excitability. J Am Heart Assoc. 2016;5:e002865.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP. hERG K(+) channels: structure, function, and clinical significance. Physiol Rev. 2012;92:1393–478.

    Article  CAS  PubMed  Google Scholar 

  • Volders PG, Sipido KR, Carmeliet E, Spatjens RL, Wellens HJ, Vos MA. Repolarizing K+ currents ITO1 and IKs are larger in right than left canine ventricular midmyocardium. Circulation. 1999a;99:206–10.

    Article  CAS  PubMed  Google Scholar 

  • Volders PG, Sipido KR, Vos MA, et al. Downregulation of delayed rectifier K(+) currents in dogs with chronic complete atrioventricular block and acquired torsades de pointes. Circulation. 1999b;100:2455–61.

    Article  CAS  PubMed  Google Scholar 

  • Volders PG, Stengl M, van Opstal JM, et al. Probing the contribution of IKs to canine ventricular repolarization: key role for beta-adrenergic receptor stimulation. Circulation. 2003;107:2753–60.

    Article  PubMed  Google Scholar 

  • Waldo AL, Camm AJ, deRuyter H, et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD investigators. Survival with oral d-Sotalol. Lancet (London, England). 1996;348:7–12.

    Article  CAS  Google Scholar 

  • Wang Q, Curran ME, Splawski I, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996;12:17–23.

    Article  PubMed  Google Scholar 

  • Wang W, Watanabe M, Nakamura T, Kudo Y, Ochi R. Properties and expression of Ca2+−activated K+ channels in H9c2 cells derived from rat ventricle. Am J Phys. 1999a;276:H1559–66.

    CAS  Google Scholar 

  • Wang Z, Feng J, Shi H, Pond A, Nerbonne JM, Nattel S. Potential molecular basis of different physiological properties of the transient outward K+ current in rabbit and human atrial myocytes. Circ Res. 1999b;84:551–61.

    Article  CAS  PubMed  Google Scholar 

  • Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H. International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels. Pharmacol Rev. 2005;57:463–72.

    Article  CAS  PubMed  Google Scholar 

  • Weiss JN, Qu Z, Shivkumar K. Electrophysiology of hypokalemia and hyperkalemia. Circ Arrhythm Electrophysiol. 2017;10(3)

    Google Scholar 

  • Wettwer E, Amos GJ, Posival H, Ravens U. Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin. Circ Res. 1994;75:473–82.

    Article  CAS  PubMed  Google Scholar 

  • Wiedmann F, Schmidt C, Lugenbiel P, et al. Therapeutic targeting of two-pore-domain potassium (K(2P)) channels in the cardiovascular system. Clin Sci. 2016;130:643–50.

    Article  CAS  Google Scholar 

  • Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92:1954–68.

    Article  CAS  PubMed  Google Scholar 

  • Winckels SK, Thomsen MB, Oosterhoff P, et al. High-septal pacing reduces ventricular electrical remodeling and proarrhythmia in chronic atrioventricular block dogs. J Am Coll Cardiol. 2007;50:906–13.

    Article  PubMed  Google Scholar 

  • Winther SV, Tuomainen T, Borup R, Tavi P, Antoons G, Thomsen MB. Potassium Channel interacting protein 2 (KChIP2) is not a transcriptional regulator of cardiac electrical remodeling. Sci Rep. 2016;6:28760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao L, Koopmann TT, Ordog B, et al. Unique cardiac Purkinje fiber transient outward current beta-subunit composition: a potential molecular link to idiopathic ventricular fibrillation. Circ Res. 2013;112:1310–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu W, Liu Y, Wang S, et al. Cytoprotective role of Ca2+-activated K+ channels in the cardiac inner mitochondrial membrane. Science. 2002;298:1029–33.

    Article  CAS  PubMed  Google Scholar 

  • Yang T, Snyders DJ, Roden DM. Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ Res. 1997;80:782–9.

    Article  CAS  PubMed  Google Scholar 

  • Yu FH, Catterall WA. The VGL-Chanome: a protein superfamily specialized for electrical Signaling and ionic homeostasis. Sci STKE. 2004;2004:re15.

    Article  PubMed  Google Scholar 

  • Zhang H, Zhu B, Yao JA, Tseng GN. Differential effects of S6 mutations on binding of quinidine and 4-aminopyridine to rat isoform of Kv1.4: common site but different factors in determining blockers’ binding affinity. J Pharmacol Exp Ther. 1998;287:332–43.

    CAS  PubMed  Google Scholar 

  • Zhang H, Flagg TP, Nichols CG. Cardiac sarcolemmal K(ATP) channels: latest twists in a questing tale! J Mol Cell Cardiol. 2010;48:71–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The helpful discussions with Dr. Kirstine Calloe are profoundly appreciated.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

    Morten B. Thomsen

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  1. Morten B. Thomsen
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Correspondence to Morten B. Thomsen .

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  1. Department of Cardiology and HCR (Heidelberg Center for Heart Rhythm Disorders), University Hospital Heidelberg, Heidelberg, Germany

    Dierk Thomas

  2. Dept. of Clinical & Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Carol Ann Remme

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Thomsen, M.B. (2018). Potassium Channels in the Heart. In: Thomas, D., Remme, C. (eds) Channelopathies in Heart Disease . Cardiac and Vascular Biology, vol 6. Springer, Cham. https://doi.org/10.1007/978-3-319-77812-9_3

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