The cardiac sodium-calcium exchanger NCX1 is a key player in the initiation and maintenance of a stable heart rhythm

Cardiovascular Research

Volumn 99, Issue 4, 2013, Pages 780-788

  Herrmann, Stefan ^a   Lipp, Peter ^b   Wiesen, Kathrina ^b   Stieber, Juliane ^a   Nguyen, Huong ^a   Kaiser, Elisabeth ^b   Ludwig, Andreas ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

Author keywords

Cardiac pacemaking; Sinoatrial node

Indexed keywords

ADENOSINE TRIPHOSPHATASE (CALCIUM); PHOSPHOLAMBAN; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SODIUM CALCIUM EXCHANGE PROTEIN; SODIUM CALCIUM EXCHANGER NCX1; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BODY WEIGHT; BRADYCARDIA; CALCIUM TRANSPORT; CONTROLLED STUDY; DISEASE SEVERITY; ELECTROSTIMULATION; HEART ARRHYTHMIA; HEART DILATATION; HEART MUSCLE CONDUCTION SYSTEM; HEART PACING; HEART RATE; HEART RHYTHM; HEART VENTRICLE CONTRACTION; HEART VENTRICLE REMODELING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SINUS NODE;

CARDIAC PACEMAKING; SINOATRIAL NODE;

ANIMALS; ARRHYTHMIAS, CARDIAC; CALCIUM; HEART RATE; MICE; MICE, INBRED C57BL; MYOCARDIUM; SINOATRIAL NODE; SODIUM-CALCIUM EXCHANGER; VENTRICULAR REMODELING;

EID: 84883214925     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvt154     Document Type: Article

References (32)

1. Irisawa H, Brown HF, Giles W. Cardiac pacemaking in the sinoatrial node. Physiol Rev 1993;73:197-227.
2. Schram G, Pourrier M, Melnyk P, Nattel S. Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ Res 2002;90: 939-950.
3. Bogdanov KY, Vinogradova TM, Lakatta EG. Sinoatrial nodal cell ryanodine receptor and Na(+)-Ca(2+) exchanger: molecular partners in pacemaker regulation. Circ Res 2001; 88:1254-1258.
4. Honjo H, Inada S, Lancaster MK, Yamamoto M, Niwa R, Jones SA et al. Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity. Circ Res 2003;92:e41-e44.
5. Lakatta EG, Maltsev VA, Bogdanov KY, Stern MD, Vinogradova TM. Cyclic variation of intracellular calcium: a critical factor for cardiac pacemaker cell dominance. Circ Res 2003;92:e45-e50.
6. Vinogradova TM, Bogdanov KY, Lakatta EG. beta-Adrenergic stimulation modulates ryanodine receptor Ca(2+) release during diastolic depolarization to accelerate pacemaker activity in rabbit sinoatrial nodal cells. Circ Res 2002;90:73-79.
7. Bucchi A, Baruscotti M, Robinson RB, DiFrancesco D. I(f)-dependent modulation of pacemaker rate mediated by cAMP in the presence of ryanodine in rabbit sino-atrial node cells. J Mol Cell Cardiol 2003;35:905-913.
8. Lakatta EG, Maltsev VA, Vinogradova TM. A coupled SYSTEM of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker. Circ Res 2010;106:659-673.
9. Vinogradova TM, Lyashkov AE, ZhuW, Ruknudin AM, Sirenko S, YangDet al. High basal protein kinase A-dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells. Circ Res 2006;98:505-514.
10. Kurata Y, Hisatome I, Shibamoto T. Roles of sarcoplasmic reticulum Ca2+ cycling and Na+/Ca2+ exchanger in sinoatrial node pacemaking: insights from bifurcation analysis of mathematical models. Am J Physiol Heart Circ Physiol 2012;302:H2285-H2300.
11. Imtiaz MS, von derWeid PY, Laver DR, van Helden DF. SRCa2+ store refill-A key factor in cardiac pacemaking. J Mol Cell Cardiol 2010;49:412-426.
12. Bogdanov KY, Maltsev VA, Vinogradova TM, Lyashkov AE, Spurgeon HA, SternMDet al. Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state. Circ Res 2006;99:979-987.
13. Reuter H, Henderson SA, Han T, Ross RS, Goldhaber JI, Philipson KD. The Na+-Ca2+ exchanger is essential for the action of cardiac glycosides. Circ Res 2002;90:305-308.
14. Koushik SV,Wang J, Rogers R, Moskophidis D, Lambert NA, Creazzo TL et al. Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization. FASEB J 2001;15:1209-1211.
15. Cho CH, Kim SS, Jeong MJ, Lee CO, Shin HS. The Na+-Ca2+ exchanger is essential for embryonic heart development in mice. Mol Cells 2000;10:712-722.
16. Wakimoto K, Kobayashi K, Kuro OM, Yao A, Iwamoto T, Yanaka N et al. Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat. J Biol Chem 2000;275:36991-36998.
17. Hoesl E, Stieber J, Herrmann S, Feil S, Tybl E, Hofmann F et al. Tamoxifen-inducible gene deletion in the cardiac conduction system. J Mol Cell Cardiol 2008;45:62-69.
18. Henderson SA, Goldhaber JI, So JM, Han T, Motter C, Ngo A et al. Functional adult myocardium in the absence of Na+-Ca2+ exchange: cardiac-specific knockout of NCX1. Circ Res 2004;95:604-611.
19. Herrmann S, Layh B, Ludwig A. Novel insights into the distribution of cardiacHCNchannels: an expression study in the mouse heart. J Mol Cell Cardiol 2011;51:997-1006.
20. Herrmann S, Fabritz L, Layh B, Kirchhof P, Ludwig A. Insights into sick sinus syndrome from an inducible mouse model. Cardiovasc Res 2011;90:38-48.
21. CaroniP, Carafoli E.AnATP-dependent Ca2+-pumping system in dog heart sarcolemma. Nature 1980;283:765-767.
22. Eisner DA, Sipido KR. Sodiumcalcium exchange in the heart: necessity or luxury? Circ Res 2004;95:549-551.
23. Mattick P, Parrington J, Odia E, Simpson A, Collins T, Terrar D. Ca2+-stimulated adenylyl cyclase isoform AC1 is preferentially expressed in guinea-pig sino-atrial node cells and modulates the I(f) pacemaker current. J Physiol 2007;582:1195-1203.
24. Younes A, Lyashkov AE, Graham D, Sheydina A, Volkova MV, Mitsak M et al. Ca(2+)-stimulated basal adenylyl cyclase activity localization in membrane lipid microdomains of cardiac sinoatrial nodal pacemaker cells. J Biol Chem 2008;283:14461-14468.
25. Gao Z, Rasmussen TP, Li Y, KutschkeW, Koval OM, Wu Y et al. Genetic inhibition of Na(+)-Ca(2+) exchanger current disables fight or flight sinoatrial node activity without affecting resting heart rate. Circ Res 2013;112:309-317.
26. Boyett MR, Honjo H, Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res 2000;47:658-687.
27. Herrmann S, Stieber J, Stockl G, Hofmann F, Ludwig A.HCN4provides a 'depolarization reserve' and is not required for heart rate acceleration in mice. EMBO J 2007;26: 4423-4432.
28. Bround MJ, Asghari P,Wambolt RB, Bohunek L, Smits C, PhilitMet al. Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice. Cardiovasc Res 2012;96: 372-380.
29. Lakatta EG, Vinogradova TM, Maltsev VA. The missing link in the mystery of normal automaticity of cardiac pacemaker cells. Ann N Y Acad Sci 2008;1123:41-57.
30. Sanders L, Rakovic S,LoweM, Mattick PA,TerrarDA. Fundamental importance ofNa+-Ca2+ exchange for the pacemaking mechanism in guinea-pig sino-atrial node. J Physiol 2006;571:639-649.
31. Groenke SL, Eric D, Zhang R, Nakano H, Jordan MC, Roos KP et al. The Na+-Ca2+ exchanger is required for sinoatrialnode pacemaker activity inmurine myocardium. Biophys J 2011;100:247a.
32. Antoons G,Willems R, Sipido KR. Alternative strategies in arrhythmia therapy: evaluation of Na/Ca exchange as an anti-arrhythmic target. Pharmacol Therap 2012;134:26-42.