Properties and role of the delayed rectifier K^+ current in the pacemaker activity

本研究采用膜片钳全细胞技术研究了豚鼠窦房结起搏细胞延迟整流钾电流（I_K）的特性和作用。在有和无甲磺酰苯胺类I_2<Kr>阻断剂E-4031（5 μM）的情况下进行的尾包络试验表明，豚鼠SA结细胞中的I_2由药物敏感的、快速激活的和耐药的、缓慢激活的I_2组成<Kr><Ks>。E<Ks>-4031敏感电流（半激活电压V1/2为-26.2 mV）的激活范围远小于<Ks>E-4031电阻电流（V1/2为+17.2 mV）的激活范围。在<Kr>电位为正至-50 mV时，I_2表现出明显的内向整流，而<Ks>I_3仅表现出轻微的整流。I_2的尾电流幅值<Kr>与I_3的尾电流幅值相当<Ks>， ...更多信息 在100 ms去极化脉冲至+20 mV后复极化至-50 mV时测量，模拟动作电位。在电流钳实验中，E-4031（0.5和5 μM）的水浴应用最初将负电位下的复极化阶段延迟至约-30 mV，而对更多去极化电位下的复极化没有产生任何明显影响，并对自发动作电位中的最大舒张电位进行去极化。这些结果有力地表明，导致最大舒张电位约为-60 mV的复极晚期（电位负至-30 mV）主要由I_2产生<Kr>，而在<Kr>豚鼠窦房结细胞的自发动作电位中，I_2对复极晚期的贡献要么不存在，要么很小。虽然本研究没有完全阐明I_2在<Ks>自发动作电位中的作用，但有理由推测I_2<Ks>至少部分地对豚鼠窦房结细胞复极的早期起作用。少

The present research project was undertaken to investigate the properties and role of the delayed rectifier K^+ current (I_K) in isolated guinea-pig sino-atrial (SA) node pacemaker cells using the whole-cell configuration of the patchclamp technique. An envelope of tails test conducted in the absence and presence of a potent methanesulfonanilide I_<Kr> blocker E-4031 (5 μM) indicated that I_K comprises the drug-sensitive, rapidly activating and drug-resistant, slowly activating components of I_K (I_<Kr> and I_<Ks>, respectively) in guinea-pig SA node cells. The activation range for I_<Ks>, defined as the E-4031-sensitive current (half-activation voltage, V_<1/2>, of -26.2 mV) was much more negative than that for I_<Ks>, defined as the E-4031-resistant current (V_<1/2> of +17.2 mV). I_<Kr> exhibited a marked inward rectification at potentials positive to -50 mV, whereas I_<Ks> showed only a slight rectification. The tail current amplitude of I_<Kr> was comparable to that of I_<Ks>, when … More measured upon repolarization to -50 mV after a 100-ms depolarizing pulse to +20 mV, simulating an action potential. In the current-clamp experiment, a bath application of E-4031 (0.5 and 5 μM) initially delayed the repolarization phase at potentials negative to approximately -30 mV without producing any appreciable effect on repolarization at more depolarized potentials and depolarized the maximum diastolic potential in spontaneous action potentials. These results strongly indicate that the late phase of repolarization (at potentials negative to -30 mV) leading to the maximal diastolic potential at around -60 mV is primarily produced by I_<Kr> and that the contribution of I_<Kr> to the late repolarization is either absent or, if any, very small in spontaneous action potentials in guinea-pig SA node cells. While the present study did not fully elucidate the role of I_<Ks> in the spontaneous action potentials, it is reasonable to speculate that I_<Ks> is, at least in part, responsible for the early phase of repolarization in guinea-pig SA node cells. Less