| Title | Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes |
| Authors | Ma, Jihua Luo, Antao Wu, Lin Wan, Wei Zhang, Peihua Ren, Zhiqiang Zhang, Shuo Qian, Chunping Shryock, John C. Belardinelli, Luiz |
| Affiliation | Wuhan Univ Sci & Technol, Cardioelectrophysiol Res Lab, Coll Med, Wuhan 430081, Peoples R China. Peking Univ, Dept Cardiol, Beijing 100871, Peoples R China. Gilead Sci Inc, Dept Biol, Palo Alto, CA USA. Wuhan Univ Sci & Technol, Cardioelectrophysiol Res Lab, Coll Med, 947 Heping Ave, Wuhan 430081, Peoples R China. |
| Keywords | calcium overload sodium channel signal transduction patch-clamp technique cardiomyocyte PERSISTENT NA+ CURRENT FAILING HUMAN HEART HYDROGEN-PEROXIDE CONTRACTILE DYSFUNCTION MYOCARDIAL-ISCHEMIA CARDIAC MYOCYTES REDOX REACTION NITRIC-OXIDE RAT MODULATION |
| Issue Date | 2012 |
| Publisher | american journal of physiology cell physiology |
| Citation | AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY.2012,302,(8),C1141-C1151. |
| Abstract | Ma J, Luo A, Wu L, Wan W, Zhang P, Ren Z, Zhang S, Qian C, Shryock JC, Belardinelli L. Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes. Am J Physiol Cell Physiol 302: C1141-C1151, 2012. First published December 21, 2011; doi:10.1152/ajpcell.00374.2011.-An increase in intracellular Ca2+ concentration ([Ca2+](i)) augments late sodium current (I-Na.L) in cardiomyocytes. This study tests the hypothesis that both Ca2+-calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) mediate the effect of increased [Ca2+](i) to increase I-Na.L. Whole cell and open cell-attached patch clamp techniques were used to record I-Na.L in rabbit ventricular myocytes dialyzed with solutions containing various concentrations of [Ca2+](i). Dialysis of cells with [Ca2+](i) from 0.1 to 0.3, 0.6, and 1.0 mu M increased I-Na.L in a concentration-dependent manner from 0.221 +/- 0.038 to 0.554 +/- 0.045 pA/pF (n = 10, P < 0.01) and was associated with an increase in mean Na+ channel open probability and prolongation of channel mean open-time (n = 7, P < 0.01). In the presence of 0.6 mu M [Ca2+](i), KN-93 (10 mu M) and bisindolylmaleimide (BIM, 2 mu M) decreased I-Na.L by 45.2 and 54.8%, respectively. The effects of KN-93 and autocamtide-2-related inhibitory peptide II (2 mu M) were not different. A combination of KN-93 and BIM completely reversed the increase in I-Na.L as well as the Ca2+-induced changes in Na+ channel mean open probability and mean open-time induced by 0.6 mu M [Ca2+](i). Phorbol myristoyl acetate increased I-Na.L in myocytes dialyzed with 0.1 mu M [Ca2+](i); the effect was abolished by Go-6976. In summary, both CaMKII and PKC are involved in [Ca2+](i)-mediated augmentation of I-Na.L in ventricular myocytes. Inhibition of CaMKII and/or PKC pathways may be a therapeutic target to reduce myocardial dysfunction and cardiac arrhythmias caused by calcium overload. |
| URI | http://hdl.handle.net/20.500.11897/393487 |
| ISSN | 0363-6143 |
| DOI | 10.1152/ajpcell.00374.2011 |
| Indexed | SCI(E) |
| Appears in Collections: | 待认领 |
