Pacemaker mechanism of porcine sinoatrial node cells

1)背景窦房结细胞外向钾电流：众所周知，在心脏细胞中，在其他电压和时间依赖的电流系统的阻断下，时间无关的外向电流激发正电位。在大鼠心房细胞中，4-氨基吡啶敏感的K~(++)电流作为本底电流，而在兔窦房结细胞中，4-氨基吡啶敏感的K~(++)电流起背景电流的作用。我们认为背景电流在窦房结细胞复极中起重要作用。2)T型钙离子通道在心脏起搏中的作用：观察米贝地尔对兔窦房结细胞离子电流的影响，并与其他二氢吡啶和镍离子进行比较。米贝法地尔、伊福地平和尼伐地平均阻断肌电活动，使自发活动频率减慢，同时维持动作电位的幅度。另一方面，氨氯地平，一种选择性的…More&gt；阻滞剂通过降低波幅抑制动作电位。I&lt；CAT&gt；阻断剂NI^&lt；2+&>(50μM)仅使频率降低20%。我们认为，非米地平的心动过缓作用至少部分来源于对钙、钙、钙的抑制。3)药物引起的动作电位延长利培酮：利培酮是一种终止精神分裂症急性发作和预防精神分裂症复发的常用药物。另一方面，吸入麻醉剂阻断IKs并使动作电位明显延长。4)基于离子通道和离子转运体的动力学和密度，我们构建了窦房结细胞的仿真模型。该模型包括15个已知存在于兔窦房结细胞的离子通道和转运体，并复制了自发动作电位。较少

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