Calmodulin regulation of excitation-contraction coupling in cardiac myocytes | |
Yang, DM ; Song, LS ; Zhu, WZ ; Chakir, K ; Wang, W ; Wu, CH ; Wang, YB ; Xiao, RP ; Chen, SRW ; Cheng, H | |
刊名 | circulation research |
2003 | |
关键词 | calmodulin Ca2+/calmodulin-dependent protein kinase II L-type Ca2+ channels phospholamban CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE CA2+ RELEASE RYANODINE RECEPTOR CALCIUM CHANNELS MUSCLE PHOSPHOLAMBAN INACTIVATION BINDING PHOSPHORYLATION APOCALMODULIN |
DOI | 10.1161/01.RES.0000064566.91495.0C |
英文摘要 | Calmodulin (CaM) as a ubiquitous Ca2+ sensor interacts with multiple key molecules involved in excitation-contraction (EC) coupling. In the present study, we report that adenoviral expression of a mutant CaM lacking all of its four Ca2+-binding sites, CaM(1-4), at a level 6.5- fold over endogenous CaM markedly increases the amplitude and abbreviates the decay time of Ca2+ transients and contraction in cultured rat ventricular myocytes. To determine the underlying mechanisms, we examined the properties of L-type Ca2+ channels, Ca2+/CaM-dependent protein kinase II (CaMKII), and phospholamban (PLB) in the sarcoplasmic reticulum (SR). We found that CaM(1-4) expression markedly augmented L-type Ca2+ current amplitude and slowed its inactivation. Surprisingly, overexpression of CaM(1-4) increased CaMKII activity and phosphorylation of PLB-Thr-17. Moreover, CaM(1-4) elevated diastolic Ca2+ and caffeine-labile Ca2+ content of the SR. Inhibition of CaMKII by KN-93 or a myristoylated autocamtide-2 related inhibitory peptide prevented the aforementioned PLB phosphorylation and reversed the positive inotropic and relaxant effects, indicating that CaMKII is essential to CaM(1-4) actions. These results demonstrate that CaM modulates Ca2+ influx, SR Ca2+ release, and Ca2+ recycling during cardiac EC coupling. A novel finding of this study is that expression of a Ca2+-insensitive CaM mutant can lead to activation of CaMKII in cardiac myocytes.; Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease; SCI(E); PubMed; 15; ARTICLE; 6; 659-667; 92 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/346698] |
专题 | 生命科学学院 |
推荐引用方式 GB/T 7714 | Yang, DM,Song, LS,Zhu, WZ,et al. Calmodulin regulation of excitation-contraction coupling in cardiac myocytes[J]. circulation research,2003. |
APA | Yang, DM.,Song, LS.,Zhu, WZ.,Chakir, K.,Wang, W.,...&Cheng, H.(2003).Calmodulin regulation of excitation-contraction coupling in cardiac myocytes.circulation research. |
MLA | Yang, DM,et al."Calmodulin regulation of excitation-contraction coupling in cardiac myocytes".circulation research (2003). |
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