CGRP对大鼠心肌细胞动作电位时程的影响及KATP通道在其中的作用

Effect of calcitonin gene-related peptide on action potential duration in rat cardiomyocytes and role of KATP channels

目的评价降钙素基因相关肽(CGRP)对大鼠心室肌细胞动作电位时程(APD)的影响及KATP通道在其中的作用。方法酶解法急性分离SD大鼠心室肌细胞(n=6)。采用给药前后自身对照的方法,先给予单纯台式液灌流2 min,随后依次给予含CGRP 10-10 mol/L、CGRP8-3710-9 mol/L和Glibenclamide 10-5 mol/L的台式液灌流2 min,采用全细胞膜片钳技术记录APD和确定KATP通道电流密度,并计算APD90。结果与单独台式液灌流比较,给予CGRP后心室肌细胞APD90缩短,KATP通道电流密度升高(P<0.05);与给予CGRP后比较,给予CGRP8-37或Glibenclamide后APD90延长,KATP通道电流密度降低(P<0.05)。结论CGRP可通过其特异性受体缩短大鼠心室肌细胞APD,KATP通道激活参与了这一过程。

Objective To evaluate the effect of calcitonin gene-related peptide(CGRP)on action potential duration(APD)in rat ventricular myocytes and the role of ATP-sensitive potassium(KATP)channels.Methods Ventricular myocytes(n=6)acutely isolated from clean-grade Sprague-Dawley rats by enzymatic hydrolysis were obtained.Using the method of self-control before and after administration,the cells were first perfused with Tyrode′s solution alone for 2 min,and then with Tyrode′s solution containing CGRP 10-10 mol/L,CGRP8-3710-9 mol/L and glibenclamide 10-5 mol/L sequentially for 2 min.The APD was recorded,and KATP channel current density was determined by whole-cell patch-clamp technique,and APD at 90%of repolarization(APD90)was calculated.Results Compared with the results after giving Tyrode′s solution alone,APD90 of ventricular myocytes was significantly shortened,and the KATP channel current density of ventricular myocytes was increased after giving CGRP(P<0.01).The APD90 of ventricular myocytes was significantly prolonged,and KATP channel current density of ventricular myocytes was decreased after giving CGRP8-37 or glibenclamide as compared with that after giving CGRP(P<0.05).Conclusion CGRP can shorten APD of rat ventricular myocytes through its specific receptor,and activation of KATP channels is involved in this process.