Study of the outward current systems of mammalian ventricular muscle cells in relation to the genesis of rhythm disturbances

应用膜片钳技术研究了哺乳动物心室肌细胞瞬时外向电流的特性及其功能作用。瞬时外向电流被认为是浦肯野细胞特有的特性，但在心室细胞中并不存在或发育不全。在本研究中，我们证明了当去极化从-60 mV或更负的保持电位施加到正-20 mV的电压时，在兔的心室肌细胞中存在I&lt；to-Gt；。在阻断钙电流后，这种电流仍被激活，表明该电流是钙不敏感的电流。电流表现出缓慢的恢复动力学，时间常数约为2秒。由于I&lt；到&gt；的缓慢恢复动力学，耦合间隔较短的过早兴奋表现出…的增大更多的平台和延长的动作电位时程，面对钙电流的快速恢复，充分分析了电压和时间相关的激活和失活及其动力学，这种电流的载流子主要是K+，部分是Na+。4-氨基吡啶(4-AP)很容易阻断这个组分，还有一种对4-AP敏感但能被咖啡因阻断的组分。咖啡因敏感的咖啡因对&gt；的动力学比钙不敏感的快，且随着脉搏的增加而增加。该电流可被细胞内EGTA和外加Ryanodine或Sr^&lt；2+&gt；所阻断。这些结果表明，电流是对&gt；敏感的。在心率较快时，对钙敏感的心肌细胞参与了心室复极，而对钙不敏感的心肌细胞则显示心率。当心率突然加快或休息后开始快速刺激时，对钙敏感和对钙不敏感的电流与钙电流一起参与动作电位的改变。为了进一步传递其性质，这种对钙敏感的离子的单通道记录尚未成功，目前正在进行研究。较少

The properties and functional roles of the transient outward current in mammalian ventricular muscle cells were studied using the patch clamp technique applied to isolated rabbit ventricular myocytes. The transient outward current (I_<to>) has been assumed to be a unique Property of purkinje cells but not to be present or underdeveloped in ventricular cells. In this study, we demonstrated the presence of I_<to> in rabbit ventricular myocytes when depolarization was applied from the holding potential at -60 mV or more negative to voltages positive to -20 mV. The current was shown to contribute to the formation of small phase l and notch on ventricular action potentials.This I_<to> was activated even after blocking the Ca^<2+> current, indicating this I_<to> as Ca^<++>-insensitive one. The current exhibited a slow recovery kinetics showing the time constant around 2 sec. Because of this slow recovery kinetics of I_<to>, premature excitations with short coupling intervals showed augmented … More plateau and prolonged action potential duration, in the face of the rapid recovering the Ca^<2+> current.The voltage- and time-dependent activation and inactivation, and their kinetics were fully analyzed.The charge carrier of this I_<to> was mainly K^+ and partly Na^+. This I_<to> component was easily blocked by 4-aminopyridine (4-AP).There was another type of I_<to> which was sensitive to 4-AP but was blocked by caffeine. The caffeine-sensitive I_<to> had faster kinetics than those of Ca^<2+>-insensitive I_<to> and increased with rapid pulsations. The current was abolished by intracellular EGTA, and by external application of ryanodine or Sr^<2+> for Ca^<2+>. These results indicate the current as Ca^<2+>-sensitive I_<to>. The Ca^<2+>-sensitive I_<to> contributes to ventricular repolarization at fast heart rate, whereas the Ca^<2+>-insensitive one to show heart rate. The Ca^<2+>-sensitive and -insensitive I_<to> together with the Ca^<2+> current were shown to contribute to the action potential alterations when the heart rate was suddenly increased or a rapid stimulation was initiated after a rest. The single channel recording of this Ca^<2+>-sensitive I_<to> for the further deliveation of its properties has not been succeeded and the study is currently undertaken. Less