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Pacemaker mechanism of porcine sinoatrial node cells

猪窦房结细胞的起搏机制

基本信息

批准号：
13670034
负责人：
ONO Kyoichi
金额：
$ 2.5万
依托单位：
Akita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670034/
关键词：
sinoatrial node background K current TASK pacemaker current sustained inward current Delayed rectifier K current T-type Ca current L-type Ca current 自動能イオンチャネルシミュレーションリスペリドン活動電位カリウムチャネルラット

项目摘要

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

1)背景窦房结细胞外向K^+电流：众所周知，在其他电压和时间依赖性电流系统的阻断下，心肌细胞时间无关的外向电流存在正电位。我们证明，在大鼠心房细胞中，被称为TASK的4个跨膜K^+电流作为背景电流，而在兔窦房结细胞中，4-氨基吡啶敏感的K^+电流起这一作用。我们认为背景电流对窦房结细胞的复极起重要作用。2) t型Ca^<2+>通道在心脏起搏中的作用：对比其他二氢吡啶类药物和Ni^<2+>，研究米贝替拉迪对家兔窦房结细胞离子电流的影响。米贝替拉地尔、依福尼地平和尼伐地平均阻断I_<CaL>、I_<CaT>和I_<st3>，在维持动作电位幅度的同时，减慢了自发活动的频率。另一方面，选择性i <CaL…More >阻滞剂氨氯地平通过降低振幅抑制动作电位。Ni^<2+> (50 μM), I_<CaT>阻滞剂，仅降低了20%的频率。我们认为，埃福米地平的心动过缓作用至少部分来源于抑制I_<ca, tbb0。此外，电压和频率依赖性的I_<ca, l>的抑制和Ist的阻断可能有助于减缓起搏器去极化。3)利培酮药物诱导的动作电位延长：利培酮是一种常用于终止精神分裂症急性精神病发作和预防精神病发作复发的药物，可选择性抑制豚鼠心室细胞IKr。另一方面，吸入麻醉剂阻断IKs，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，构建了窦房结细胞的模拟模型。该模型包括兔窦房结细胞中已知的15种离子通道和转运体，并再现了自发动作电位。少