Inhibitory action of troglitazone, an insulin-sensitizing agent, on the calcium current in cardiac ventricular cells of guinea pig.
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 - 50 mV than at - 80 mV. The half-maximum inhibiting concentration (IC50) of troglitazone was 0.8 microM with the Hill coefficient of 0.84 at -50 mV HP. In contrast, the IC50 value was higher than 10 microM at -80 mV HP. These results suggest that troglitazone at therapeutic concentrations inhibit the Ca2+ channels and may exert cardioprotective effects in diabetic conditions.
Katoh
Y
Y
Department of Internal Medicine III, Fukushima Medical University, School of Medicine, 1 Hikarigaoka, Japan.
Hashimoto
S
S
Kimura
J
J
Watanabe
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone