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

应用膜片钳技术对兔心室肌细胞进行分离，研究了哺乳动物心室肌细胞瞬态外向电流的特性和功能作用。暂态外向电流（I_<至>）被认为是浦肯野细胞的独特特性，但在心室细胞中并不存在或不发达。在这项研究中，我们证明了当从负60 mV或更负的保持电位到正20 mV的电压去极化时，兔心室肌细胞中存在I_<至>。电流被证明有助于形成小的i相和心室动作电位缺口。即使在阻断Ca^<2+>电流后，I_<到>也被激活，这表明I_<到>是Ca^<++>不敏感的I_<到>。Ca^<2+>电流的快速恢复，使得Ca^<2+>电流具有较长的平台期和较长的动作电位持续时间。充分分析了电压和时间依赖性的激活和失活及其动力学。I_<到>的载流子主要是K^+，部分是Na^+。该I_<to>组分容易被4-氨基吡啶（4-AP）阻断。另一种类型的I_<to>对4-AP敏感，但被咖啡因阻断。与Ca^<2+>-不敏感的I_< >相比，咖啡因对>敏感的I_<具有更快的动力学，并随着快速脉动而增加。细胞内EGTA和外用ryanodine或Ca^<2+>的Sr^<2+>消除电流。这些结果表明电流为Ca^<2+>-对>敏感I_<。Ca^<2+>-敏感的I_<对>敏感有助于快速心率时的心室复极，而Ca^<2+>-不敏感的I_<显示心率。当心率突然增加或休息后开始快速刺激时，Ca^<2+>电流与Ca^<2+>电流共同导致动作电位的改变。这种Ca^<2+>-敏感的I_<对>的单通道记录尚未成功，以进一步传递其性质，目前正在进行研究。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