Functional role of background K+current in pacemaker cells of sinoatrial.node

背景钾电流在窦房结起搏细胞中的功能作用

基本信息

批准号：
15590182
负责人：
ONO Kyouichi
金额：
$ 2.24万
依托单位：
Akita University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590182/
关键词：
sinoatrial node Pacemaker mechanism background K^+ current TASK Ca^<2+> channel delayed rectifier K^+ current QT prolongation 外向き電流カルシウム電流イオンチャネル自動能

项目摘要

This project was carried out to characterize the background K^+ current in cardiac myocytes, particularly in pacemaker cells of sinoatrial node in relation to its possible contribution to the pacemaker activity. The following results were obtained.1)Species and regional heterogeneity of background K^+ current.In rat atrial cells, the background K^+ current was increased by increasing external pH, and inhibited by bupivacaine or metanandamide. In addition, the K^+ current was enhanced by halothane. All these properties were similar to TASK, a member of 4 TM K^+ channels. Thus, TASK may play a role for repolarization of rat atrial myocytes. On the other hand, the background K^+ current in rabbit sinoatrial node (SAN) cells was insensitive to metanandamide, and was inhibited by 4-aminopyridine. In porcine SAN cells, the background current was significantly smaller than that of rabbit. These findings indicate that the difference in the current density of the K^+ current contributes to different firing frequency among various mammalian species.2)Action potential of porcine sinoatrial node cells.The action potential (AP) duration of porcine SAN cells is significantly longer than that of rabbit, leading to slower heart rate in pigs. We have shown that, in addition to the lack of the background K^+ current, window component of the L-type Ca^<2+> current helps to prolong the AP duration. The L-type Ca^<2+> channel in SAN cells is kinetically and biologically different from that of ventricular cells.3)Effects of inhalational anesthetics on delayer rectifier K^+ currentSevoflurane, a most popular inhalational anesthetics in Japan, activates the background K^+ current. Also the anesthetics is shown to inhibit the slowly activating delayed rectifier K^+ current. The inhibition occurs at clinically relevant concentrations. The resulting prolongation of ventricular repolarization may partly account for the clinical observation of excessive QT prolongation by these anesthetics.

该项目的目的是表征心肌细胞中的背景 K^+ 电流，特别是窦房结起搏器细胞中的背景 K^+ 电流及其对起搏器活动的可能贡献。得到如下结果：1)背景K^+电流的物种和区域异质性。在大鼠心房细胞中，背景K^+电流随着外部pH值的增加而增加，而布比卡因或间氨酰胺则抑制背景K^+电流。此外，氟烷增强了 K^+ 电流。所有这些属性都与 TASK 类似，TASK 是 4 个 TM K^+ 通道的成员。因此，TASK可能在大鼠心房肌细胞的复极化中发挥作用。另一方面，兔窦房结(SAN)细胞中的背景K^+电流对metanandamide不敏感，并且被4-氨基吡啶抑制。在猪SAN细胞中，背景电流明显小于兔的。这些结果表明，K^+电流的电流密度差异导致不同哺乳动物物种之间的放电频率不同。2）猪窦房结细胞的动作电位。猪SAN细胞的动作电位（AP）持续时间明显更长比兔子的心率慢，导致猪的心率较慢。我们已经表明，除了缺乏背景K^+电流之外，L型Ca^<2+>电流的窗口分量有助于延长AP持续时间。 SAN细胞中的L型Ca^2+通道在动力学和生物学上与心室细胞不同。3)吸入麻醉药对延迟整流器K^+电流的影响日本最流行的吸入麻醉药七氟烷激活背景K^+电流。此外，麻醉剂可以抑制缓慢激活的延迟整流器 K^+ 电流。抑制作用发生在临床相关浓度下。由此产生的心室复极延长可能部分解释了临床观察到这些麻醉药导致 QT 过度延长的原因。