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）背景在辛里尔节点细胞中的k^+电流：众所周知，在心脏不依赖的外向主义外观势势中，封闭了电压和时间依赖性电流系统。 ^ +电流称为任务，充当背景电流，而在兔子促源细胞中4-氨基吡啶敏感的K^ +电流起着这种作用。 T型Ca^<2+>心脏起搏器的作用：Mibefradil对兔子促淋巴结的离子电流的影响与其他二摩托尿和Ni^<2+>相比。 <cal>，另一方面，I_ <ST3>动作电位。至少部分地源自I_ <Ca，T>的抑制，i_ <ca，l>的自由度触发到了起搏器去极化的速度。3）由药物利培酮诱导：精神分裂症患者的精神病发作复发，在豚鼠心室细胞中有选择地抑制IKR。节点细胞包括15个离子通道和已知存在于兔子节点细胞中的转运蛋白，并重现了自发作用的电位。