Physiological Modulations of Cardiac K^+ Currents by Ca^<2+> and their Roles for Arrhythmogenesis

本研究采用全细胞膜片钳技术研究了豚鼠和家兔心室肌细胞的两种类型的钾电流。一种是在兔心肌细胞上记录到的瞬时外向钾电流（I_k<to>），另一种是在豚鼠心肌细胞上记录到的延迟外向钾电流（I_k）。在<to>-20 mV的阶跃去极化作用下，I_2被激活。I_2<to>由Ca^&lt;2+&gt;不敏感成分和Ca^&lt;2+&gt;敏感成分组成。对Ca^&lt;2+&gt;不敏感的I_2<to>易被4-氨基吡啶阻断，而对Ca^&lt;2+&gt;敏感的I_2易被咖啡因抑制。后一种成分也可通过去除细胞外Ca^&lt;2+&gt;或应用Ca^&lt;2+&gt;阻断剂而消除。应用ryanidine可抑制该作用。这些结果表明，Ca^&lt;2+&gt;敏感性I_2<to>是通过Ca^&lt;2 +&gt;通道的Ca ^&lt;2 +&gt;内流和/或通过Ca^&lt;2 +&gt;依赖性通道的Ca^&lt;2+&gt;增加而激活的。 ...更多信息 在快速刺激时，Ca^&lt;2+&gt;敏感性I_K<to>增加，使动作电位复极切迹的形成和心动过速时动作电位复极的缩短，在-50 mV时，I_K被正性去极化激活，使动作电位复极终相出现。从尾电流的动力学分析，I_k被分为两个具有快速和缓慢激活的分量。快激活I_k对Ca^&lt;2+&gt;内流敏感。因此，无论是用无Ca^2+溶液还是应用Ca^2+拮抗剂抑制Ca^2+内流，都能产生反常的动作电位时程延长，这归因于对快激活I_k的抑制。I_k和动作电位复极的行为可以通过改变细胞内Ca^&lt;2+&gt;对I_k的调节来很好地模拟。Co^&lt;2+&gt;通常用作Ca^&lt;2+&gt;通道的阻滞剂，但在相当浓度下它也抑制I_k。Co^&lt;2+&gt;阻断I_k的机制可能与屏蔽表面负电荷、减少功能通道和增加电压依赖性过程有关。因此，Co^&lt;2+&gt;通过多种机制阻断I_k。少

In this research project, we studied two types of K+ currents in isolated vetricular myocytes from guinea-pig and rabbit hearts using the patch-clamp technique of the whole-cell configurations. The one type was the transient outward current (I_<to>) recorded from rabbit myocytes and the other was the delayed outward K^+ current (I_k) from guinea-pig myocytes. I_<to> was activated by step depolarizations positive to -20 mV I_<to> was found to be composed of two components, the Ca^<2+>-insensitive and Ca^<2+>-sensitive components. The Ca^<2+>-insensitive I_<to> was easily blocked by 4-aminopyridine and the Ca^<2+>-sensitive one was inhibited by caffeine. The latter component was also abolished by removing extracellular Ca^<2+> or application of Ca^<2+> blocking agents. It was inhibited by application of ryanidine. All of these results suggest that the Ca^<2+>-sensitive I_<to> was activated by Ca^<2+>-influx via the Ca^<2+> channel and/or increased internal Ca^<2+> through the Ca^<2+> rel … More ease from SR. The Ca^<2+>-sensitive I_<to> was increased during rapid stimulation and, therefore, it contributed the formation of the notch on action potential repolarization and its shortening during tachycardia.I_K was activated by depolarization positive to -50 mV and it contributed to the final repolarization phase. From the kinetic analysis of the tail current, I_k was separated by two components with a rapid and slow activation. The fast activating I_k was sensitive to Ca^<2+>-influx. Therefore, the inhibition of the Ca^<2+>-influx either by Ca^<2+> free solution or application of the Ca^<2+> antagonists produced a paradoxical prolongation of action potential duration, which was attributed to suppression of the fast activating I_k. The behaviors of I_k and action potential repolarizations were well simulated by the modulation of I_k by changes in internal Ca^<2+>. Co^<2+> was often used as a blocker of the Ca^<2+> channel but it also inhibited I_k at comparable concentrations. The mechanisms of the I_k block by Co^<2+> were shown to be screening the negative surface charges, decreasing the functional channel and additional voltage-dependent process. Therefore, Co^<2+> blocked I_k by multiple mechanisms. Less