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

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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