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

哺乳动物心室肌细胞外向电流系统与节律紊乱发生关系的研究

• 批准号: 62480214
• 负责人: HIRAOKA Masayasu
• 金额: $ 3.58万
• 依托单位: Tokyo Medical and Dental University, Medical Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480214/
• 关键词: Single ventricular myocyte; Patch clamp method; Transient outward current; Inactivation process; 心室再分極相; パッチクランプ法; 活動電位再分極; 単ー心室筋細胞; Ca^<2+>ー非感受性一過外向き電流; Ca^<2+>ー感受性; 心室筋再分極相; Ca^<2+>電流

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

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（I_<to>）被认为是浦肯野细胞的一种独特特性，但在心室细胞中不存在或不发达。在本研究中，我们证明了在<to>兔心室肌细胞中，当从-60 mV或更负的保持电位施加到-20 mV的正电压时，存在I_2。该电流可促进心室肌细胞动作电位小I相和切迹的形成，<to>即使在阻断Ca^&lt;2+&gt;电流后，该I_仍被激活，表明该I_<to>是Ca^&lt;++&gt;不敏感的I_。电流表现出缓慢的恢复动力学，显示时间常数约为2秒。由于这种缓慢的恢复动力学<to>，具有短耦合间隔的过早激发表现出增强， ...更多信息 结果表明，在Ca^2+电流迅速恢复的情况下，I_2的激活和失活均呈现电压依赖性和时间依赖性，其电荷载体<to>主要为K^+，部分为Na^+。此I_2<to>组分易被4-氨基吡啶（4-AP）阻断，另一种I_2组分<to>对4-AP敏感，但可被咖啡因阻断。咖啡因敏感的I_2<to>比Ca^&lt;2+&gt;不敏感的I_2具有更快的动力学，并且<to>随着快速脉动而增加。细胞内EGTA可阻断该电流，而外源性ryanodine或Sr^&lt;2+&gt;可阻断Ca^&lt;2 +&gt;。这些结果表明电流是Ca^&lt;2+&gt;敏感的I_<to>。在快心率时，Ca^&lt;2+&gt;敏感性I_2<to>参与心室复极，而Ca^&lt;2+&gt;不敏感性I_2参与心率。当心率突然增加或休息后开始快速刺激时，Ca^&lt;2+&gt;敏感性和非敏感性I_2<to>与Ca^&lt;2+&gt;电流一起参与动作电位的改变。单道记录这种Ca^&lt;2+&gt;敏感性I_2以<to>进一步研究其性质尚未成功，目前正在进行研究。少

项目成果

Kawano, S.; M. Hiraoka: "Transient outward current and action potential alterations after initiation of rapid stimulation in rabbit ventricular myocytes."

河野，S.；

Hiraoka, M.; S. Kawano: "Two types of transient outward current in rabbit ventricular myocytes." J. Mol. Cell Cardiol.19 (Suppl.1). 33- (1987)

平冈，M.；

Kawano,S.;M.Hiraoka: Am.J.Physiol.

Kawano，S.；M.Hiraoka：Am.J.Physiol。

M.Hiraoka: Jpn.Circ.J.51. 963 (1987)

M.Hiraoka：Jpn.Circ.J.51。

Hiraoka,M.;S.Kawano: J.Mol.Cell.Cardiol.20(Suppl.1). S40 (1988)

Hiraoka，M.；S.Kawano：J.Mol.Cell.Cardiol.20（增刊1）。