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发动蛋白诱导的囊泡内陷参与介导一氧化氮合酶对心肌收缩的调控

刘锴, 李俊, 陈义汉^*

同济大学医学院，上海 200092；心律失常教育部重点实验室(同济大学)，上海 200120

摘要

一氧化氮合酶(nitric oxide synthase, NOS)系统对正常或应激状态下心脏电-机械活动起着复杂的调控作用。本研究采用心肌细胞收缩与钙瞬变同步检测手段，研究NOS系统对心肌细胞收缩的潜在调控机制。在急性分离的正常大鼠心室肌细胞，100 µmol/L spermidine选择性抑制神经源性一氧化氮合酶(neuronal NOS, nNOS)显著加强了细胞的收缩活动[正常对照组：(10.5 ± 0.21)%；nNOS抑制组：(12.4 ± 0.18)%]与内质网的钙释放[正常对照组：(0.27 ± 0.03)%；nNOS抑制组：(0.42 ± 0.01)%]，但是延缓了心肌细胞的舒张[正常对照组：(25.2 ± 1.3) ms；nNOS抑制组：(53 ± 2.8) ms]与内质网的钙回收[正常对照组：(129 ± 4.3) ms；nNOS抑制组：(176 ± 7.1) ms]。该效应与30 µmol/L dynasore抑制内陷调节蛋白——发动蛋白的结果类似。NO供体S-Nitroso-N-acetylpenicillamine (SNAP)可以缓解nNOS抑制或发动蛋白抑制所致的收缩与内质网钙释放加强的效应。结果表明，nNOS系统对心脏机械活动的调节可能部分涉及发动蛋白介导的内陷机制。

关键词： 肌细胞; 心脏; 收缩; 一氧化氮合酶

分类号：R33

[Dynamin-mediated endocytic process contributes to neuronal nitric oxide synthase-mediated regulation of cardiac contraction.] [Article in Chinese]

LIU Kai, LI Jun, CHEN Yi-Han^*

Tongji University School of Medicine, Shanghai 200092, China； Key Laboratory of Arrhythmias, Ministry of Education, Tongji University, Shanghai 200120, China

Abstract

Nitric oxide synthases (NOSs) play complex roles in the regulation of cardiac excitation contraction coupling under basal and stressed conditions. Herein, using the recording approach for intracellular calcium transient and synchronous myocyte contraction, the potential mechanism for NOSs-mediated cardiomyocyte contraction was explored. We found that selective inhibition of neuronal NOS (nNOS) with 100 µmol/L spermidine markedly enhanced the cardiomyocyte twitch [control: (10.5 ± 0.21)%; nNOS inhibition: (12.4 ± 0.18)%] and calcium transient [control: (0.27 ± 0.03)%; nNOS inhibition: (0.42 ± 0.01)%], but slowed the relengthening of twitch [control: (25.2 ± 1.3) ms; nNOS inhibition: (53 ± 2.8) ms] and the calcium transient decay [control: (129 ± 4.3) ms; nNOS inhibition: (176 ± 7.1) ms], which was similar to that by dynamin inhibition with 30 µmol/L dynasore. The nNOS inhibition- or dynasore-mediated effects could be rescued by an NO donor, S-Nitroso-N-acetylpenicillamine (SNAP). Our data suggest that the selective nNOS-mediated regulation of cardiac contractile activity may partly involve the dynamin-mediated endocytic mechanism.

Key words: myocytes, cardiac; contraction; nitric oxide synthase;

收稿日期：2011-02-18　　录用日期：2011-04-08

通讯作者：陈义汉　　E-mail: yihanchen@tongji.edu.cn

引用本文：

刘锴, 李俊, 陈义汉. 发动蛋白诱导的囊泡内陷参与介导一氧化氮合酶对心肌收缩的调控[J]. 生理学报 2011; 63 (3): 211-218.

LIU Kai, LI Jun, CHEN Yi-Han. [Dynamin-mediated endocytic process contributes to neuronal nitric oxide synthase-mediated regulation of cardiac contraction.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (3): 211-218 (in Chinese with English abstract).