Pacemaker mechanism of porcine sinoatrial node cells

1)窦房结细胞外向K^+电流的背景：众所周知，在心脏细胞中，在其他电压和时间依赖性电流系统的阻断下，时间非依赖性外向电流存在正电位。我们证明，在大鼠心房细胞中，四个跨膜K^+电流（称为ASK）作为背景电流，而在兔窦房结细胞中，4-氨基吡啶敏感性K^+电流起着这种作用。2）T型Ca^<2+>通道在心脏起搏中的作用：观察了米贝拉地尔对兔窦房结细胞离子电流的影响，并与其他二氢吡啶类药物和Ni^<2+>进行了比较。米贝拉地尔、依福地平和尼伐地平均能阻断<CaL>I_1、<CaT>I_2和I_3<st3>，减慢自发活动的频率，同时维持动作电位的幅度。另一方面，选择性I_&lt;CaL ...更多信息 &gt;阻断剂，通过降低幅度抑制动作电位。I_2受体阻断剂Ni^（2+）（50 μM）<CaT>仅使频率降低20%。我们认为，依咪地平的心动过缓作用至少部分来自于抑制I_&lt;ca，T&gt;。3）利培酮引起的药物性动作电位延长：利培酮是治疗精神分裂症的常用药物，它选择性地抑制豚鼠心室肌细胞IKr。另一方面，吸入麻醉药阻断IKs，使动作电位明显延长。4）在离子通道和离子转运蛋白动力学和密度的基础上，构建了窦房结细胞的模拟模型。该模型包括已知存在于兔窦房结细胞中的15个离子通道和转运蛋白，并再现了自发动作电位。少

1) Background outward K^+ current in sinoatrial node cells: It is well known that in cardiac cells time-independent outward current extists positive potentials under the blockade of other voltage- and time-dependent current systems. We demonstrated that in rat atrial cells four transmembrane K^+ current, termed as TASK, acts as a background current whereas in rabbit sinoatrial node cells 4-aminopyridine-sensitive K^+ current plays this role. We consider that the background current plays an important role for repolarization of sinoatrial node cells.2) Role of T-type Ca^<2+> channel in cardiac pacemaking: Effect of mibefradil on ionic currents of rabbit sinoatrial node cells were investigated in comparison to other dihyropiridines and Ni^<2+>. Mibefradil, efonidipine and nilvadipine, all of which blocked I_<CaL>, I_<CaT>, and I_<st3>, slowed the frequency of the spontaneous activity while maintaining the amplitude of the action potential. On the other hand, amlodipine, a selective I_<CaL … More > blocker, suppressed the action potential by reducing the amplitude. Ni^<2+> (50 μM), a I_<CaT> blocker, decreased the frequency only 20 %. We consider that the bradycardic action of efomidipine was derived, at least in part, from the suppression of I_<ca,T>. In addition, voltage- and frequency-dependent inhibition of I_<ca,L> and the block of Ist might contribute to the slowing of the pacemaker depolarization.3) Drug-induced prolongation of action potential induced by drugs risperidone: Risperidone, a commonly used for terminating acute psychotic episodes and preventing recurrence of psychotic episodes in schizophrenics, inhibited IKr selectively in guinea-pig ventricular cells. On the other hand, inhalational anesthetics blocked IKs and produced a marked prolongation of the action potential.4) On the basis of kinetics and density of ionic channels and ion transporters, we constructed a simulation model for sinoatrial node cells. The model includes 15 ionic channels and transporters known to be present in rabbit sinoatrial node cells, and reproduced the spontaneous action potential. Less