Ca2+/calmodulin potentiates I Ks in sinoatrial node cells by activating Ca2+/calmodulin-dependent protein kinase II

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• 作者：Yu Xie ; Wei-Guang Ding…
• 关键词：Calmodulin ; CaMKII ; Sinoatrial node cells ; Delayed rectifier K+ current ; KCNQ1
• 刊名：Pflügers Archiv - European Journal of Physiology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：467
• 期：2
• 页码：241-251
• 全文大小：782 KB
• 参考文献：1. Aiba T, Hesketh GG, Liu T, Carlisle R, Villa-Abrille MC, O'Rourke B, Akar FG, Tomaselli GF (2010) Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes. Cardiovasc Res 85(3):454-63 CrossRef
  2. Anderson ME, Braun AP, Wu Y, Lu T, Wu Y, Schulman H, Sung RJ (1998) KN-93, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early after depolarizations in rabbit heart. J Pharmacol Exp Ther 287(3):996-006
  3. Anderson ME, Brown JH, Bers DM (2011) CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol 51(4):468-73 CrossRef
  4. Ashpole NM, Herren AW, Ginsburg KS, Brogan JD, Johnson DE, Cummins TR, Bers DM, Hudmon A (2012) Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates cardiac sodium channel NaV1.5 gating by multiple phosphorylation sites. J Biol Chem 287(24):19856-9869 CrossRef
  5. Bai CX, Namekata I, Kurokawa J, Tanaka H, Shigenobu K, Furukawa T (2005) Role of nitric oxide in Ca2+ sensitivity of the slowly activating delayed rectifier K+ current in cardiac myocytes. Circ Res 96(1):64-2 CrossRef
  6. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (1996) K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384(6604):78-0 CrossRef
  7. Boucherot A, Schreiber R, Kunzelmann K (2001) Regulation and properties of KCNQ1 (K(V)LQT1) and impact of the cystic fibrosis transmembrane conductance regulator. J Membr Biol 182(1):39-7
  8. Braun AP, Schulman H (1995) The multifunctional calcium/calmodulin-dependent protein kinase: from form to function. Annu Rev Physiol 57:417-45 CrossRef
  9. DiFrancesco D, Ferroni A, Mazzanti M, Tromba C (1986) Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node. J Physiol 377:61-8 CrossRef
  10. Ding WG, Toyoda F, Matsuura H (2002) Blocking action of chromanol 293B on the slow component of delayed rectifier K(+) current in guinea-pig sino-atrial node cells. Br J Pharmacol 137(2):253-62 CrossRef
  11. Doerr T, Denger R, Trautwein W (1989) Calcium currents in single SA nodal cells of the rabbit heart studied with action potential clamp. Pflugers Arch 413(6):599-03 CrossRef
  12. Fabiato A (1981) Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol 78(5):457-97 CrossRef
  13. Gamper N, Li Y, Shapiro MS (2005) Structural requirements for differential sensitivity of KCNQ K+ channels to modulation by Ca2+/calmodulin. Mol Biol Cell 16(8):3538-551 CrossRef
  14. Ghosh S, Nunziato DA, Pitt GS (2006) KCNQ1 assembly and function is blocked by long-QT syndrome mutations that disrupt interaction with calmodulin. Circ Res 98(8):1048-054 CrossRef
  15. Hagiwara N, Irisawa H, Kameyama M (1988) Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells. J Physiol 395:233-53 CrossRef
  16. Irisawa H, Brown HF, Giles W (1993) Cardiac pacemaking in the sinoatrial node. Physiol Rev 73(1):197-27
  17. Kerst G, Beschorner U, Unsold B, von Hahn T, Schreiber R, Greger R, Gerlach U, Lang HJ, Kunzelm
• 作者单位：Yu Xie (1)
  Wei-Guang Ding (1)
  Hiroshi Matsuura (1)
  
  1. Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

The slow component of the delayed rectifier K+ current (I Ks) plays an important role in the repolarization of action potentials in cardiac pacemaker cells and ventricular myocytes, and is regulated by various signaling pathways. Recent evidence has shown that calmodulin (CaM) is involved in modulation of diverse ion channels in cardiac myocytes under physiological and pathophysiological conditions. In the present study, we examined regulation of I Ks by Ca2+/CaM in guinea pig sinoatrial (SA) node cells using the whole-cell patch-clamp method. The density of I Ks was larger during intracellular dialysis with a higher Ca2+ concentration (pCa 7, Ca (+)) compared to that with a low Ca2+ concentration (pCa 10, Ca (?). Intracellular application of CaM (400?nM) markedly potentiated I Ks with a Ca (+) pipette solution but not with a Ca (? solution, thus showing that CaM potentiates I Ks in an intracellular Ca2+-dependent manner. Intracellular application of a specific Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, autocamtide-2 inhibitory peptide (AIP, 500?nM), markedly reduced I Ks activity in the presence of higher intracellular Ca2+. Similarly, bath application of another inhibitor, KN-93 (1?μM) also significantly suppressed I Ks. Finally, the stimulatory action on I Ks of Ca2+/CaM was abolished by pretreatment with KN-93. Taken together, these observations suggest that Ca2+/CaM stimulates I Ks in guinea pig SA node cells through activation of CaMKII. This enhancement of I Ks by CaMKII may be involved in modulation of SA node automaticity under physiological or pathophysiological condition.