激活δ阿片受体可抑制大鼠心室肌细胞L-型钙电流和瞬时外向钾电流(英文)  

Activation of δ-opioid receptors inhibits L-type Ca^(2+) current and transient outward K+ current in rat ventricular myocytes

作　　者：林媛媛[1] 武冬梅[2] 刘磊[1] 刘清华[1] 闫喆一[1] 吴博威[1] 

机构地区：[1]山西医科大学生理学教研室,太原030001 [2]山西医科大学药理学教研室,太原030001

出　　处：《生理学报》2008年第1期38-42,共5页Acta Physiologica Sinica

基　　金：supported by Open Fund for Key Laboratory in Shanxi Province (No. 200503011)

摘　　要：本研究采用全细胞膜片钳技术观察了SNC162 (一种选择性δ阿片受体激动剂)对大鼠心室肌细胞L型钙电流(L-type Ca2+current, ICa-L)和瞬时外向钾电流(transient outward K+ current, Ito)的影响。结果显示,SNC162 明显抑制大鼠心室肌细胞 ICa-L 和Ito,对 ICa-L 和 Ito 的最大抑制率分别为(46.13±4.12)% 和(36.53±10.57)%。1×10-4 mol/L SNC162 使 ICa-L 的平均电流密度从(8.98±0.40) pA/pF下降到(4.84±0.44) pA/pF (P<0.01, n=5),Ito 的平均电流密度从(18.69±2.42) pA/pF降低到(11.73±1.67) pA/pF (P<0.01,n=5)。单独应用 naltrindole (一种选择性δ阿片受体拮抗剂)对大鼠心室肌细胞 ICa-L 和 Ito 无显著作用,但预先应用 naltrindole 可以消除SNC162 对ICa-L和Ito 的抑制作用。结果表明,通过δ阿片受体,SNC162 (1×10-6~1×10-4 mol/L)浓度依赖性地抑制大鼠心室肌细胞ICa-L 和 Ito,这可能是激动δ阿片受体产生抗心律失常效应的重要机制。In the present study, whole-cell patch-clamp technique was used to observe the effects of SNC162, a selective agonist of δ-opioid receptors, on L-type Ca^2＋ current （ICa-L） and transient outward K^＋ current （Ito） in rat ventricular myocytes. The results showed that SNC 162 significantly inhibited ICa-L and Ito in rat ventricular myocytes. The maximal inhibition rate of ICa-L and Ito reached （46.13±4.12）% and （36.53±10.57）%, respectively. SNC162 at 1×10^-4 mol/L inhibited the current density of ICa-L from （8.98±0.40） pA/pF to （4.84±0.44） pA/pF （P〈0.01, n=5） and inhibited that of/to from （18.69±2.42） pA/pF to （11.73±1.67） pA/pF （P〈0.01, n=5）. Furthermore, the effects of naltrindole, a highly selective antagonist of δ-opioid receptors, on ICa-L and/to were also observed. The results showed that naltrindole alone had no effects on ICa-L and/to, while it abolished the inhibitory effects of SNC162 on ICa-L and Ito. In conclusion, SNC162 concentration-dependently inhibited ICa-L and/to in rat ventricular myocytes via activation of the δ-opioid receptors, which may be a fundamental mechanism underlying the antiarrhythmic effect of activating δ-opioid receptors.

关 键 词：SNC162 膜片钳技术 心肌细胞 NALTRINDOLE 

分 类 号：R541[医药卫生—心血管疾病]