Protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes.
The protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in single guinea pig ventricular myocytes was studied. Whole-cell patch clamp technique was used to study the effect of H2O2 (0.5 mmol/L) on L-type calcium current in single guinea pig ventricular myocytes and the action of pretreatment with carvedilol (0.5 micromol/L). 0.5 micromol/L carvedilol had no significant effect on ICa,L and its channel dynamics. In the presence of 0.5 mmol/L H2O2, peak current of ICa,L was reduced significantly (P<0.001), the I-V curve of ICa,L was shifted upward, steady-state activation curve and steady-state deactivation curve of ICa,L were shifted left and recovery time of ICa,L was delayed significantly (P<0.001). 0.5 micromol/L carvedilol significantly alleviated the inhibitory effect of H2O2 on ICa,L as compared with that in H2O2 group (P<0.01). In addition, carvedilol reversed the changes of dynamics of ICa,L induced by H2O2. It was concluded that carvedilol could alleviate the abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes. It shows partly the possible mechanism of the special availability of carvedilol in chronic heart failure.
Liu
Nian
N
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yu
Ronghui
R
Ruan
Yanfei
Y
Zhou
Qiang
Q
Pu
Jun
J
Li
Yang
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D005260:Female; D005609:Free Radicals / Q000009:adverse effects*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D011412:Propanolamines / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D005609:Free Radicals; D011412:Propanolamines; D000077261:Carvedilol