Frequency-dependent acceleration of relaxation in the heart depends on CaMKII, but not phospholamban
Frequency-dependent acceleration of relaxation in the heart depends on CaMKII, but not phospholamban
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DOI：
10.1006/jmcc.2002.2034
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发表时间：
2002-08-01
影响因子：
5
通讯作者：
Bers, DM
中科院分区：
文献类型：
--
作者：
DeSantiago, J;Maier, LS;Bers, DM
德桑蒂亚戈湖S. Maier和D. M. BERS。心脏舒张的频率依赖性加速依赖于CaMKII，而不是Phospholamban。分子和细胞心脏病学杂志（2002）34，975-984。频率依赖性舒张加速（FDAR）是一种内在的生理机制，它允许在更高的心率下更快的心室舒张充盈。FDAR也可在离体心肌小梁和心肌细胞中观察到，但其机制仍不清楚。我们测试的假设，FDAR结果主要来自钙/钙调蛋白依赖性蛋白激酶II（CaMKII）依赖刺激肌浆网（SR）钙转运，但不需要受磷蛋白。实验在2 - 3或35 degreesC在分离的心室肌和单个肌细胞从野生型（WT）和受磷蛋白基因敲除（PLB-KO）小鼠和大鼠心室肌细胞。在不存在和存在CaMKII抑制剂（1 μ（M）KN-93或20 μ（M）autocamtide-2相关抑制肽，AIP）的情况下，测量肌肉的等长收缩力和无负荷缩短以及肌细胞中的Ca瞬变（[Ca]（o）= 1 m（M））。刺激频率在宽范围（0.2-8 Hz）内改变，还比较了休息后与稳态抽搐。在WT和PLB-KO小鼠肌肉中，抽搐力的FDAR是突出的，但在很大程度上被KN-93抑制。在PLB-KO心肌细胞中，抽搐收缩的FDAR与Ca瞬变的FDAR相关，并且两者都被KN-93抑制。类似地，不同的CaMKII抑制剂（AIP）抑制大鼠心室肌细胞收缩和Ca瞬变的FDAR。我们得出结论，FDAR的结果主要来自钙调素激酶II依赖刺激SR钙转运，但不需要受磷蛋白。(C)2002爱思唯尔科技有限公司版权所有。
J. DESANTIAGO, L. S. MAIER AND D. M. BERS. Frequency-dependent Acceleration of Relaxation in the Heart Depends on CaMKII, but not Phospholamban. Journal of Molecular and Cellular Cardiology (2002) 34, 975-984. Frequency-dependent acceleration of relaxation (FDAR) is an intrinsic physiological mechanism, which allows more rapid ventricular diastolic filling at higher heart rates. FDAR is also observed in isolated myocardial trabeculae and cardiac myocytes, but its mechanism is still poorly understood. We tested the hypothesis that FDAR results mainly from Ca/ calmodulin-dependent protein kinase II (CaMKII) dependent stimulation of sarcoplasmic reticulum (SR) Ca transport, but does not require phospholamban. Experiments were performed at 2 3 or 35degreesC in isolated ventricular muscle and single myocytes from wild-type (WT) and phospholamban knockout (PLB-KO) mice and rat ventricular myocytes. Isometric twitch force of muscles and unloaded shortening and Ca transients in myocytes were measured ([Ca](o) = 1 m(M)) in the absence and presence of CaMKII inhibitors (1 mu(M) KN-93 or 20 mu(M) autocamtide-2 related inhibitory peptide, AIP). Stimulation frequency was altered over a wide range (0.2-8 Hz) and post-rest vs steady state twitches were also compared. In both WT and PLB-KO mouse muscles FDAR of twitch force was prominent, but was largely suppressed by KN-93. FDAR of twitch contractions was associated with FDAR of Ca transients in PLB-KO myocytes, and both were inhibited by KN-93. Similarly, a different CaMKII inhibitor (AIP) inhibited FDAR of contraction and Ca transients in rat ventricular myocytes. We conclude that FDAR results mainly from CaMKII-dependent stimulation of SR Ca transport, but does not require phospholamban. (C) 2002 Elsevier Science Ltd. All rights reserved.