Suppression of Early and Late Afterdepolarizations by Heterozygous Knockout of the Na+/Ca2+ Exchanger in a Murine Model

Circulation: Arrhythmia and Electrophysiology

Volumn 8, Issue 5, 2015, Pages 1210-1218

  Bögeholz, Nils ^a   Pauls, Paul ^a,b   Bauer, B Klemens ^a,b   Schulte, Jan S ^b   Dechering, Dirk G ^a   Frommeyer, Gerrit ^a   Kirchhefer, Uwe ^b   Goldhaber, Joshua I ^c,d   Müller, Frank U ^b   Eckardt, Lars ^a   Pott, Christian ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b Institute of Pharmacology and Toxicology   (United States)

^c UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^d CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

action potentials; arrhythmias, cardiac; heart failure; Na + Ca 2+ exchanger

Indexed keywords

CAFFEINE; ETHYLENE GLYCOL 1,2 BIS(2 AMINOPHENYL) ETHER N,N,N',N' TETRAACETIC ACID; RYANODINE RECEPTOR; SODIUM CALCIUM EXCHANGE PROTEIN;

ACTION POTENTIAL DURATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL ISOLATION; CONTROLLED STUDY; DELAYED AFTERDEPOLARIZATION; EARLY AFTERDEPOLARIZATION; HEART ARRHYTHMIA; HEART DEPOLARIZATION; HEART MUSCLE CELL; HETEROZYGOTE; KNOCKOUT MOUSE; MEMBRANE STEADY POTENTIAL; MOUSE; MURINE MODEL; NONHUMAN; PERFORATED PATCH CLAMP; PRIORITY JOURNAL; WILD TYPE; ACTION POTENTIAL; ANIMAL; DISEASE MODEL; GENETICS; HEART FAILURE; IMMUNOBLOTTING; METABOLISM; PATCH CLAMP TECHNIQUE; PATHOPHYSIOLOGY; PHYSIOLOGY;

ACTION POTENTIALS; ANIMALS; ARRHYTHMIAS, CARDIAC; DISEASE MODELS, ANIMAL; HEART FAILURE; HETEROZYGOTE; IMMUNOBLOTTING; MICE; MICE, KNOCKOUT; MYOCYTES, CARDIAC; PATCH-CLAMP TECHNIQUES; SODIUM-CALCIUM EXCHANGER;

EID: 84944685761     PISSN: 19413149     EISSN: 19413084     Source Type: Journal    
DOI: 10.1161/CIRCEP.115.002927     Document Type: Article

References (35)

1. Pogwizd SM, Schlotthauer K, Li L, Yuan W, Bers DM. Arrhythmogenesis and contractile dysfunction in heart failure: roles of sodium-calcium exchange, inward rectifier potassium current, and residual beta-adrenergic responsiveness. Circ Res. 2001;88:1159-1167.
2. Marban E, Robinson SW, Wier WG. Mechanisms of arrhythmogenic delayed and early afterdepolarizations in ferret ventricular muscle. J Clin Invest. 1986;78:1185-1192. doi: 10.1172/JCI112701.
3. January CT, Riddle JM. Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current. Circ Res. 1989;64:977-990.
4. Volders PG, Kulc?ar A, Vos MA, Sipido KR, Wellens HJ, Lazzara R, Szabo B. Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes. Cardiovasc Res. 1997;34:348-359.
5. Pott C, Muszynski A, Ruhe M, Bögeholz N, Schulte JS, Milberg P, Mönnig G, Fabritz L, Goldhaber JI, Breithardt G, Schmitz W, Philipson KD, Eckardt L, Kirchhof P, Müller FU. Proarrhythmia in a non-failing murine model of cardiac-specific Na+/Ca2+ exchanger overexpression: whole heart and cellular mechanisms. Basic Res Cardiol. 2012;107:247. doi: 10.1007/s00395-012-0247-7.
6. Pogwizd SM, Qi M, Yuan W, Samarel AM, Bers DM. Upregulation of Na+/Ca2+ exchanger expression and function in an arrhythmogenic rabbit model of heart failure. Circ Res. 1999;85:1009-1019.
7. de Groot SH, Schoenmakers M, Molenschot MM, Leunissen JD, Wellens HJ, Vos MA. Contractile adaptations preserving cardiac output predispose the hypertrophied canine heart to delayed afterdepolarization-dependent ventricular arrhythmias. Circulation. 2000;102:2145-2151.
8. Mészáros J, Khananshvili D, Hart G. Mechanisms underlying delayed afterdepolarizations in hypertrophied left ventricular myocytes of rats. Am J Physiol Heart Circ Physiol. 2001;281:H903-H914.
9. Sipido KR, Volders PG, de Groot SH, Verdonck F, Van de Werf F, Wellens HJ, Vos MA. Enhanced Ca2+ release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis. Circulation. 2000;102:2137-2144.
10. Bers DM, Pogwizd SM, Schlotthauer K. Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure. Basic Res Cardiol. 2002;97 Suppl 1:I36-I42.
11. Janse MJ. Electrophysiological changes in heart failure and their relationship to arrhythmogenesis. Cardiovasc Res. 2004;61:208-217.
12. Pogwizd SM, Bers DM. Cellular basis of triggered arrhythmias in heart failure. Trends Cardiovasc Med. 2004;14:61-66. doi: 10.1016/j.tcm.2003.12.002.
13. Beuckelmann DJ, Näbauer M, Erdmann E. Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure. Circ Res. 1993;73:379-385.
14. Jordan MC, Henderson SA, Han T, Fishbein MC, Philipson KD, Roos KP. Myocardial function with reduced expression of the sodiumcalcium exchanger. J Card Fail. 2010;16:786-796. doi: 10.1016/j.cardfail.2010.03.012.
15. Kirchhefer U, Neumann J, Baba HA, Begrow F, Kobayashi YM, Reinke U, Schmitz W, Jones LR. Cardiac hypertrophy and impaired relaxation in transgenic mice overexpressing triadin 1. J Biol Chem. 2001;276:4142-4149. doi: 10.1074/jbc.M006443200.
16. Pott C, Yip M, Goldhaber JI, Philipson KD. Regulation of cardiac L-type Ca2+ current in Na+-Ca2+ exchanger knockout mice: functional coupling of the Ca2+ channel and the Na+-Ca2+ exchanger. Biophys J. 2007;92:1431-1437. doi: 10.1529/biophysj.106.091538.
17. Pott C, Goldhaber JI, Philipson KD. Homozygous overexpression of the Na+-Ca2+ exchanger in mice: evidence for increased transsarcolemmal Ca2+ fluxes. Ann N Y Acad Sci. 2007;1099:310-314. doi: 10.1196/annals.1387.019.
18. Henderson SA, Goldhaber JI, So JM, Han T, Motter C, Ngo A, Chantawansri C, Ritter MR, Friedlander M, Nicoll DA, Frank JS, Jordan MC, Roos KP, Ross RS, Philipson KD. Functional adult myocardium in the absence of Na+-Ca2+ exchange: cardiac-specific knockout of NCX1. Circ Res. 2004;95:604-611. doi: 10.1161/01. RES.0000142316.08250.68.
19. Reuter H, Henderson SA, Han T, Matsuda T, Baba A, Ross RS, Goldhaber JI, Philipson KD. Knockout mice for pharmacological screening: testing the specificity of Na+-Ca2+ exchange inhibitors. Circ Res. 2002;91:90-92.
20. Tanaka H, Nishimaru K, Aikawa T, Hirayama W, Tanaka Y, Shigenobu K. Effect of SEA0400, a novel inhibitor of sodium-calcium exchanger, on myocardial ionic currents. Br J Pharmacol. 2002;135:1096-1100. doi: 10.1038/sj.bjp.0704574.
21. Barrientos G, Bose DD, Feng W, Padilla I, Pessah IN. The Na+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate (KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels. Mol Pharmacol. 2009;76:560-568. doi: 10.1124/mol.109.057265.
22. Birinyi P, Acsai K, Bányász T, Tóth A, Horváth B, Virág L, Szentandrássy N, Magyar J, Varró A, Fülöp F, Nánási PP. Effects of SEA0400 and KBR7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes. Naunyn Schmiedebergs Arch Pharmacol. 2005;372:63-70. doi: 10.1007/s00210-005-1079-x.
23. Milberg P, Pott C, Frommeyer G, Fink M, Ruhe M, Matsuda T, Baba A, Klocke R, Quang TH, Nikol S, Stypmann J, Osada N, Müller FU, Breithardt G, Noble D, Eckardt L. Acute inhibition of the Na+/Ca2+ exchanger reduces proarrhythmia in an experimental model of chronic heart failure. Heart Rhythm. 2012;9:570-578. doi: 10.1016/j.hrthm.2011.11.004.
24. Nagy ZA, Virág L, Tóth A, Biliczki P, Acsai K, Bányász T, Nánási P, Papp JG, Varró A. Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed after depolarization in canine heart. Br J Pharmacol. 2004;143:827-831. doi: 10.1038/sj.bjp.0706026.
25. Pott C, Philipson KD, Goldhaber JI. Excitation-contraction coupling in Na+-Ca2+ exchanger knockout mice: reduced transsarcolemmal Ca2+ flux. Circ Res. 2005;97:1288-1295. doi: 10.1161/01.RES.0000196563.84231.21.
26. Reuter H, Han T, Motter C, Philipson KD, Goldhaber JI. Mice overexpressing the cardiac sodium-calcium exchanger: defects in excitationcontraction coupling. J Physiol. 2004;554(Pt 3):779-789. doi: 10.1113/jphysiol.2003.055046.
27. Adachi-Akahane S, Lu L, Li Z, Frank JS, Philipson KD, Morad M. Calcium signaling in transgenic mice overexpressing cardiac Na+-Ca2+ exchanger. J Gen Physiol. 1997;109:717-729.
28. 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;87:73-79.
29. Nuyens D, Stengl M, Dugarmaa S, Rossenbacker T, Compernolle V, Rudy Y, Smits JF, Flameng W, Clancy CE, Moons L, Vos MA, Dewerchin M, Benndorf K, Collen D, Carmeliet E, Carmeliet P. Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome. Nat Med. 2001;7:1021-1027. doi: 10.1038/nm0901-1021.
30. Orth PM, Hesketh JC, Mak CK, Yang Y, Lin S, Beatch GN, Ezrin AM, Fedida D. RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents. Cardiovasc Res. 2006;70:486-496. doi: 10.1016/j.cardiores.2006.01.026.
31. Qu Z, Xie LH, Olcese R, Karagueuzian HS, Chen PS, Garfinkel A, Weiss JN. Early afterdepolarizations in cardiac myocytes: beyond reduced repolarization reserve. Cardiovasc Res. 2013;99:6-15. doi: 10.1093/cvr/cvt104.
32. Sipido KR, Bito V, Antoons G, Volders PG, Vos MA. Na/Ca exchange and cardiac ventricular arrhythmias. Ann N Y Acad Sci. 2007;1099:339-348. doi: 10.1196/annals.1387.066.
33. Isaev D, Solt K, Gurtovaya O, Reeves JP, Shirokov R. Modulation of the voltage sensor of L-type Ca2+ channels by intracellular Ca2+. J Gen Physiol. 2004;123:555-571. doi: 10.1085/jgp.200308876.
34. Bogeholz N, Eckardt L, Pott C. Advantages and limitations of transgenic mice: the role of the Na+/Ca2+ exchanger in cardiac electrophysiology and arrhythmia. Curr Med Chem. 2014;21:1330-1335.
35. Waldeyer C, Fabritz L, Fortmueller L, Gerss J, Damke D, Blana A, Laakmann S, Kreienkamp N, Volkery D, Breithardt G, Kirchhof P. Regional, age-dependent, and genotype-dependent differences in ventricular action potential duration and activation time in 410 Langendorffperfused mouse hearts. Basic Res Cardiol. 2009;104:523-533. doi: 10.1007/s00395-009-0019-1.