SEARCH

SEARCH BY CITATION

Keywords:

  • adrenergic activation;
  • calcium channel blockers;
  • calcium current;
  • dog myocytes;
  • isoproterenol;
  • patch clamp

Abstract

Aim

The aim of this work was to study antagonistic interactions between the effects of various types of Ca2+ channel blockers and isoproterenol on the amplitude of L-type Ca2+ current in canine ventricular cells.

Methods

Whole-cell version of the patch clamp technique was used to study the effect of isoproterenol on Ca2+ current in the absence and presence of Ca2+ channel–blocking agents, including nifedipine, nisoldipine, diltiazem, verapamil, CoCl2 and MnCl2.

Results

Five micromolar Nifedipine, 1 μM nisoldipine, 10 μM diltiazem, 5 μM verapamil, 3 mM CoCl2 and 5 mM MnCl2 evoked uniformly a 90–95% blockade of Ca2+ current in the absence of isoproterenol. Isoproterenol (100 nM) alone increased the amplitude of Ca2+ current from 6.8 ± 1.3 to 23.7 ± 2.2 pA/pF in a reversible manner. Isoproterenol caused a marked enhancement of Ca2+ current even in the presence of nifedipine, nisoldipine, diltiazem and verapamil, but not in the presence of CoCl2 or MnCl2.

Conclusion

The results indicate that the action of isoproterenol is different in the presence of organic and inorganic Ca2+ channel blockers. CoCl2 and MnCl2 were able to fully prevent the effect of isoproterenol on Ca2+ current, while the organic Ca2+ channel blockers failed to do so. This has to be born in mind when the effects of organic Ca2+ channel blockers are evaluated either experimentally or clinically under conditions of increased sympathetic tone.