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

1 Troglitazone, an insulin-sensitizing agent shown to improve cardiac function in both experimental animals and patients with diabetes, inhibits voltage-dependent L-type Ca2+ currents (I-Ca,I-L) in cardiac myocytes, which may underlie its cardioprotective effects. However, inhibition by troglitaizone of I-Ca,I-L in diabetic cardiac myocytes has not been characterized. 2 Using whole-cell voltage-clamp techniques, I-Ca,I-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,I-L. 4 Troglitazone decreased amplitude Of I-Ca,I-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 mumol l(-1), respectively. 5 Troglitazone at 5 mumol l(-1) did not significantly influence the voltage dependency of steady-state inactivation or the inactivation time course of I-Ca,I-L in either control or diabetic myocytes. 6 Since troglitazone inhibits I-Ca,I-L more effectively in STZ-induced diabetic ventricular myocytes, this agent may prevent cardiac dysfunction in diabetes.