Osterrieder W, Brum G, Hescheler J, Trautwein W, Flockerzi V, Hofmann F
Nature. 1982 Aug 5;298(5874):576-8. doi: 10.1038/298576a0.
beta-Adrenergic stimulation of the heart is thought to increase cardiac muscle contractility by activation of cyclic AMP-dependent protein kinase and concomitant increase in the phosphorylation of certain proteins (for refs see refs 1-6). Electrophysiological studies have shown that the stimulation of cardiac beta-adrenoreceptors, the external application of cyclic AMP or its analogues to Purkinje fibres, or the injection of cyclic AMP into single myocytes can increase the slow inward current (Isi) during the plateau phase of the action potential (AP). In heart muscle this current is mainly carried by Ca2+ (refs 10, 11) and it has been suggested that cyclic AMP-dependent phosphorylation of some component of the calcium channel increases the amount of Ca2+ which enters the cell during depolarization. We have investigated this hypothesis by examining the electrical responses of isolated guinea pig ventricular myocytes to pressure injections of subunits of the cyclic AMP-dependent protein kinase. We report here that injection of the catalytic subunit (C) resulted in a lengthening of the action potential duration (APD) and an increase in the height of the plateau as well as the amplitude of Isi. By contrast, the injection of regulatory subunit (R) shortened the APD of fast and slow response APs, an effect which was reversed by adrenaline.
心脏的β-肾上腺素能刺激被认为是通过激活环磷酸腺苷（cAMP）依赖性蛋白激酶以及随之增加某些蛋白质的磷酸化来增强心肌收缩力（参考文献见参考文献1 - 6）。电生理学研究表明，刺激心脏β-肾上腺素能受体、将环磷酸腺苷或其类似物施加于浦肯野纤维外部，或者向单个心肌细胞注射环磷酸腺苷，均可增加动作电位（AP）平台期的缓慢内向电流（Isi）。在心肌中，该电流主要由Ca2 +携带（参考文献10、11），并且有人提出，钙通道某些成分的cAMP依赖性磷酸化会增加去极化期间进入细胞的Ca2 +量。我们通过检测豚鼠离体心室肌细胞对压力注射cAMP依赖性蛋白激酶亚基的电反应来研究这一假设。我们在此报告，注射催化亚基（C）导致动作电位时程（APD）延长，平台期高度增加以及Isi幅度增加。相比之下，注射调节亚基（R）缩短了快速和慢速反应动作电位的APD，肾上腺素可逆转这一效应。
