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钠钙交换在早期小鼠胚胎心肌细胞自律性和动作电位中的作用

骆红艳¹, 胡新武¹, 张亮品¹, 曾莹², 关秀文^3,*

¹华中科技大学同济医学院基础医学院生理学系，武汉 430030；²华中科技大学同济医学院附属协和医院，武汉 430030；³武汉市黄陂区人民医院，武汉 430300

摘要

本文旨在研究钠钙交换体(sodium calcium exchanger, NCX)在胚胎早期发育阶段心肌细胞动作电位(action potential, AP)产生过程中的作用。酶解法获得C57小鼠胚胎发育早期的单个心肌细胞后，用全细胞膜片钳技术记录NCX特异性阻断剂KB-R7943 (5 μmol/L)和SEA0400 (1 μmol/L)给药前后心肌细胞AP变化。结果显示，KB-R7943和SEA0400对起搏细胞样心肌细胞的AP均具有显著的负性变时作用，但只对部分心室细胞样心肌细胞产生这种作用。KB-R7943对心室细胞样心肌细胞的负性变时作用伴有动作电位时程(action potential duration, APD)缩短；而SEA0400的这种负性变时作用则与舒张期自动去极化速度(velocity of diastolic depolarization, Vdd)降低相关。从胚胎龄9.5天(embryonic day 9.5, E9.5)到E10.5，KB-R7943和SEA0400对心室细胞样胚胎心肌细胞AP负性变时作用逐渐消失。以上结果提示，在胚胎早期的短期发育过程中，NCX在胚胎心肌细胞自律性和AP形成中可能发生发育依赖性变化，表明NCX在不同条件/状态的心肌细胞中具有不同的功能。

关键词： SEA0400; KB-R7943; 钠钙交换体; 胚胎心肌细胞; 动作电位

分类号：R33

Functional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage

LUO Hong-Yan¹, HU Xin-Wu¹, ZHANG Liang-Pin¹, ZENG Ying², GUAN Xiu-Wen^3,*

¹tment of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China；²Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China；³The People's Hospital of Huangpi District, Wuhan 430300, China

Abstract

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.

Key words: SEA0400; KB-R7943; sodium calcium exchanger; fetal cardiomyocytes; action potential

收稿日期：2019-12-24　　录用日期：2020-04-17

通讯作者：关秀文　　E-mail: 329703831@qq.com

DOI: 10.13294/j.aps.2020.0086

引用本文：

骆红艳, 胡新武, 张亮品, 曾莹, 关秀文. 钠钙交换在早期小鼠胚胎心肌细胞自律性和动作电位中的作用[J]. 生理学报 2020; 72 (6): 757-764.

LUO Hong-Yan, HU Xin-Wu, ZHANG Liang-Pin, ZENG Ying, GUAN Xiu-Wen. Functional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage. Acta Physiol Sin 2020; 72 (6): 757-764