Yoko Katoh1, Shigeatsu Hashimoto1, Junko Kimura2
and Tsuyoshi Watanabe1
1DepartmentÊof Internal Medicine III, 2Department of Pharmacology,
Fukushima Medical University, School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan
Abstract: We investigated the effects of troglitazone, a new orally active hypoglycemic agent, on the voltage-dependent L-type Ca2+ current in single cardiac ventricular myocytes of guinea pigs by the whole-cell voltage clamp technique. Troglitazone blocked the Ca2+ currents in a concentration-dependent manner. The inhibitory effect was more potent at the holding potential (HP) of -50ÊmV than at -80ÊmV. The half-maximum inhibiting concentration (IC50) of troglitazone was 0.8ÊmM with the Hill coefficient of 0.84 at -50ÊmV HP. In contrast, the IC50 value was higher than 10ÊmM at -80ÊmV HP. These results suggest that troglitazone at therapeutic concentrations inhibit the Ca2+ channels and may exert cardioprotective effects in diabetic conditions.
Keywords: Troglitazone, Ca2+ channel, Cardiac myocyte, Patch-clamp, Diabetes