5-Hydroxytryptamine enhances L-type calcium current in norepinephrine-induced hypertrophic ventricular myocytes  

5-羟色胺增强去甲肾上腺素诱导的肥厚心肌L-型钙电流(英文)

作　　者：招明高 梅其炳[1] 张延凤[1] 熊晓云[1] 卢宝华[1] 邢斌[1] 赵德化[1] 

机构地区：[1]第四军医大学药理学教研室,西安中国710032

出　　处：《Acta Pharmacologica Sinica》2002年第6期523-528,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China, № 39500177.

摘　　要：AIM: To study the effects of 5-hydroxytryptamine (5-HT) on L-type calcium current (ICa) in norepine-phrine (ME)- induced hypertrophic ventricular myocytes. METHODS: Left ventricular hypertrophy was induced by injecting ME intraperitoneally in rats. The single myocytes were isolated enzymatically from left ventricle. ICa was recorded with the whole-cell configuration of the patch-clamp technique. RESULTS: (1) The ratio of left heart weight to body weight (LHW/BW) was higher (P < 0.01) in the NE-treated rats compared with the control rats on d 15. LHW/BW was increased 31.8 % in NE-treated rats. (2) ICa was larger in hypertrophic cells than that in normal cells (4.5 pA/pF±0.5 pA/pF vs 3.5 pA/pF ±0.3 pA/pF, respectively, at testing potential of 0 mV; P<0.01). (3) 5-HT (1, 10μmol/L) increased ICa and decreased the peak current potential from 0 mV to-10 mV in both myocytes. The augmentation of ICa induced by 5-HT was larger in hypertrophic ones. (4) 5-HT did not markedly influence the steady-state activation kinetics. However, 5-HT shifted steady-state inactivation curve with half inactiva-tion voltage V1 2, changing from - 39.5 mV±1.8 mV to -27.8 mV±1.7 mV (P<0.05), while not changing the voltage responsiveness of calcium channel ( slope factor k was not changed markedly). CONCLUSION: 5-HT increased ICa in ventricular myocytes by changing the kinetics of steady-state inactivation. A larger alteration of ICa induced by 5-HT in hypertrophic ventricular myocytes suggests that 5-HT be more prone toinduce arrhythmia in hypertrophic heart than in normal one.目的:研究5-羟色胺(5-HT)对去甲肾上腺素(NE)诱导的大鼠肥厚心肌L-型钙电流(I_(Ca))的影响.方法:大鼠腹腔注射NE建立心肌肥厚模型;酶解分离单个心室肌细胞;全细胞膜片箝记录I_(Ca).结果:(1)腹腔注射NE第15天,大鼠左心室与体重比增加31.8％(2)肥厚心肌细胞I_(Ca)与正常心肌细胞相比,明显增加0mV时分别为4.5pA/pF±0.5pA/pF和3.5pA/pF±0.3pA/pF(P<0.01).(3)5-HT可显著增加肥厚和正常心肌细胞I_(Ca),并使最大激活电流从0mV降低至-10mV;此外,5-HT增加I_(Ca)作用在肥厚心肌细胞更为显著.(4)稳态激活和失活实验发现,5-HT对稳态激活曲线无显著影响,而影响稳态失活曲线,使半失活电压从-39.5mV±1.8mV升高至-27.8mV±1.7mV(P<0.05),而不改变钙通道电压依赖性(斜率因子k无显著变化).结论:5-HT通过改变L-型钙通道稳态失活特征而显著增加I_(Ca),此作用在肥厚心肌细胞更显著,提示在肥厚心肌5-HT更易于诱导心律失常发生.

关 键 词：SEROTONIN CARDIOMEGALY calcium channels patch-clamp techniques 

分 类 号：R96[医药卫生—药理学]