Enhanced inhibition of L-type calcium currents by troglitazone in streptozotocin-induced diabetic rat cardiac ventricular myocytes

Br J Pharmacol. 2002 Jul;136(6):803-10. doi: 10.1038/sj.bjp.0704757.

Abstract

1. Troglitazone, an insulin-sensitizing agent shown to improve cardiac function in both experimental animals and patients with diabetes, inhibits voltage-dependent L-type Ca(2+) currents (I(Ca,L)) in cardiac myocytes, which may underlie its cardioprotective effects. However, inhibition by troglitazone of I(Ca,L) in diabetic cardiac myocytes has not been characterized. 2. Using whole-cell voltage-clamp techniques, I(Ca,L) was measured in ventricular myocytes isolated from 4-6 weeks streptozotocin (STZ)-induced diabetic rats and age-matched control rats. 3. Under control conditions with CsCl internal solution, diabetic myocytes did not differ from control myocytes in membrane capacitance, current density or voltage-dependent properties of I(Ca,L). 4. Troglitazone decreased amplitude of I(Ca,L) in both control and diabetic myocytes in a concentration-dependent manner. This inhibition was more potent in diabetic than in control myocytes; half-maximum inhibitory concentrations of troglitazone measured at a holding potential of -50 mV were 4.3 and 9.5 micromol l(-1), respectively. 5. Troglitazone at 5 micromol l(-1) did not significantly influence the voltage dependency of steady-state inactivation or the inactivation time course of I(Ca,L) in either control or diabetic myocytes. 6. Since troglitazone inhibits I(Ca,L) more effectively in STZ-induced diabetic ventricular myocytes, this agent may prevent cardiac dysfunction in diabetes.

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / physiology
  • Cells, Cultured
  • Chromans / pharmacology*
  • Diabetes Mellitus, Experimental / metabolism*
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Troglitazone

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Chromans
  • Hypoglycemic Agents
  • Thiazoles
  • Thiazolidinediones
  • Troglitazone