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类α-蝎神经毒素BmKⅠ对离体大鼠心脏收缩力及电活动的特异调控

孙海英, 朱海峰, 吉永华

中国科学院上海生命科学研究院上海生理研究所. 上海 200031

摘要

本研究探讨了一种特异性钠通道调制剂(Buthus martensi Karsch,BmKⅠ)对离体大鼠心脏收缩力及电活动的调制作用.离体心脏灌流实验显示:(1)BmKⅠ(0.5-10 μmol/L)剂量依赖地增强大鼠心肌收缩力,左心室最大发展压(LVDPmax)以及dp/dtmax与对照组相比均显著增强(n=6,P＜0.05),同时可触发正性变时作用(n=6,P＜0.05);(2)大剂量BmKⅠ(20μmol/L)引起负性肌力作用及心动过缓;(3)冠脉流量随心脏收缩力的增强反而减小,应用500nmol/L BmKⅠ时冠脉流量由14.5 ml/min降至8.6 ml/min(n=6,P＜0.05);此外,心电图记录表明BmKⅠ(0.5-10μmol/L)可触发心动过速及复杂的心律失常等电活动变化;正常灌流液洗脱后BmKI引起的大鼠心脏收缩力及电活动的改变可部分恢复.由于β-肾上腺素能受体阻滞剂普奈洛尔预先应用抑制了儿茶酚胺类神经递质的释放,提示BmKⅠ引起的大鼠心脏收缩力及电活动的改变不是由于其调节儿茶酚胺类神经递质的释放及随后β-肾上腺素能受体的激活,而可能与其对心肌电压门控钠通道的调控有关

关键词： 肌力作用; 心电图; BmKⅠ; 电压门控钠通道

BmKⅠ,an α-like scorpion neurotoxin,specifically modulates isolated rat cardiac mechanical and electrical activity

Sun Haiying, Zhu Haifeng, Ji Yonghua

Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Shanghai 200031,China

Abstract

In this study, cardiotonic and cardiotoxic effects of Buthus martensi Karsch (BmK)Ⅰ, a modulator of voltage-gated sodium channels, were investigated on the isolated rat hearts. The results showed that BmKⅠ evoked complex effects characterized by a change in both cardiac mechanical and electrical activity. Langendorff perfusion showed that: ( 1 ) maximal left ventricular developed pressure (LVDPmax) and dp/dtmax were markedly increased by BmKⅠ (0.5 -10 mol/L) in a dose-dependent manner (n =6, P＜0.05), positive chronotropic effects were also induced by BmKⅠ (n=6, P＜0.05); (2) negative inotropic action and bradycardia could be elicited at a larger dose of BmKⅠ(20μ mol/L); (3) the coronary flow varied inversely with the positive inotropic effects, coronary flow reduced during positive inotropic effects from 14. 5 to 8. 6 ml/min after administration of 500 nmol/L BmKⅠ ( n = 6, P＜ 0. 05). In addition, tachycardia and complex cardiac arrhythmias were induced by BmKⅠ (0.5-10 moL/L). The modulating of BmKⅠon the heart mechanical, electrical activity could be partially recovered after washing. As propranolol was applied to block the release of catecholamines before administration of BmKⅠ, suggesting that the changes in cardiac mechanical and electrical activity induced by BmKⅠ might not due to catecholamine release from the nerve terminal and subsequent stimulation of theβ-adrenoceptor but attributable to the modulation of BmKⅠon cardiac voltage-gated sodium channels.

Key words: Inotropic effect;Electrocardiogram (ECG);;

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引用本文：

孙海英, 朱海峰, 吉永华. 类α-蝎神经毒素BmKⅠ对离体大鼠心脏收缩力及电活动的特异调控[J]. 生理学报 2003; 55 (5): .

Sun Haiying, Zhu Haifeng, Ji Yonghua. BmKⅠ,an α-like scorpion neurotoxin,specifically modulates isolated rat cardiac mechanical and electrical activity. Acta Physiol Sin 2003; 55 (5): (in Chinese with English abstract).