Inhibitory effects of serotonin on transient outward potassium current in rat ventricular myocytes  

血清素抑制大鼠心室肌细胞瞬时外向钾电流(英文)

作　　者：招明高 梅其炳[1] 张延凤[1] 邢斌[1] 李小强[1] 崔毅[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7期617-622,共6页中国药理学报（英文版）

摘　　要：AIM: To study the effects of serotonin (5-hydroxy-tryptamine, 5-HT) on transient outward potassium current (Ito) and elucidate its mechanism in rat ventricular myo-cytes. METHODS: Ito was recorded using the conven-tional whole cell patch-clamp techniques. RESULTS: Ito density in normal myocytes was similar to that in norepinephrine-induced hypertrophic myocytes. 5-HT depressed Ito in a concentration-dependent manner with the half-maximal inhibitory concentration of (40 ± 5) μmol/L and (38±7) μmol/L in normal and hypertrophic ventricular myocytes respectively. Mianserin (5-HT2 receptor antagonist), compound 46/80 (phospholipase C antagonist), and chelerythrine chloride (protein kinase C antagonist) reversed the inhibitory effects of 5-HT on Ito, while phorbol 12-myristate 13-acetate (protein kinase C agonist) enhanced the inhibitory effect of 5-HT on Ito in normal myocytes. CONCLUSION: 5-HT markedly inhibits Ito in rat ventricular myocytes. The putative signal pathway is that 5-HT activates phospholipase C, which causes inositol phospholipid hydrolysis. The activation of downstream signal molecule, protein kinase C, phosphorates substrate target proteins, which leads to inhibition of Ito in ventricular myocytes.目的:观察血清素(5-HT)对大鼠心室肌细胞瞬时外向钾电流I_(to)的影响并探讨其作用机制.方法:全细胞膜片箝技术记录I_(to).结果:I_(to)电流密度在正常心肌和肥厚心肌细胞无明显差异.在实验电压为+70mV时,5-HT浓度依赖性抑制I_(to),在正常和肥厚心肌细胞,其半数抑制浓度分别为(4O ±5)μmol/L和(38±7)μmol/L.5-HT_2受体阻断剂米胺舍林和磷脂酶C抑制剂 Compound 48/80均可逆转 5-HT抑制I_(to)的作用;蛋白激酶激动剂醋酸佛波酯显著加强5-HT的抑制作用,而蛋白激酶抑制剂白屈菜季铵碱则逆转5-HT抑制I_(to)的作用.结论:5-HT具有抑制心肌细胞I_(to)的作用.此作用是通过激动 5-HT_2受体,启动磷脂酶C信号转导途径,进一步激活蛋白激酶从而抑制心肌I_(to)。

关 键 词：SEROTONIN transient outward potassium current patch-clamp techniques CARDIOMEGALY 

分 类 号：R96[医药卫生—药理学]