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Troglitazone-induced inhibition of l-type calcium currents is augmented in streptozotocin-induced diabetic rat cardiac ventricular myocytes
Authors:M.Arikawa  N.Takahashi  T.Ooie  S.Shigematsu  M.Hara  T.Sakata  T.Saikawa
Abstract:Troglitazone, a member of the insulin-sensitizing thiazolidinediones, was shown to suppress voltage-dependent L-type calcium currents (ICa, L) in vascular smooth muscle cells. The present study was aimed to investigate whether troglitazone may inhibit ICa, L in rat cardiac ventricular myocytes and whether the extent of troglitazone-induced inhibition of the current may be different between normal and streptozotocin (STZ)-induced diabetic rats. Whole-cell patch-clamp techniques were applied in single rat ventricular myocytes. Troglitazone reduced the amplitude of ICa, L in a concentration-dependent manner in both normal and diabetic myocytes. However, the percent inhibition of ICa, L by troglitazone in concentration of 10-5mol/L measured at a holding potential of -50 mV was significantly greater in myocytes isolated from STZ-induced diabetic rats than in control rats (87%±8% vs 47%±5%, P<0.005), without difference in voltage-dependency of the inhibition. These findings demonstrate that troglitazone-induced inhibition of ICa, L is augmented in STZ-induced diabetic cardiac ventricular myocytes, thus possibly playing a role in preventing intracellular calcium overload.
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