Protective effect of carvedilol on abnormality of L-type calcium current induced by oxygen free radical in cardiomyocytes

J Huazhong Univ Sci Technolog Med Sci. 2004;24(5):433-6. doi: 10.1007/BF02831101.

Abstract

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.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Calcium Channels, L-Type / metabolism*
  • Carbazoles / pharmacology*
  • Carvedilol
  • Female
  • Free Radicals / adverse effects*
  • Guinea Pigs
  • Heart Ventricles / cytology
  • Male
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Oxidative Stress
  • Patch-Clamp Techniques
  • Propanolamines / pharmacology*

Substances

  • Adrenergic beta-Antagonists
  • Calcium Channels, L-Type
  • Carbazoles
  • Free Radicals
  • Propanolamines
  • Carvedilol