Effects of troglitazone and pioglitazone on the action potentials and membrane currents of rabbit ventricular myocytes.
The effects of the antidiabetic thiazolidinediones troglitazone and pioglitazone on action potentials and membrane currents were studied in rabbit ventricular myocytes. Troglitazone (10 microM) reversibly reduced excitability of the myocytes and modified their action potential configuration. It significantly increased the stimulation threshold required to elicit action potentials and decreased action potential amplitude and the maximum upstroke velocity of the action potentials. The Inhibition of the maximum upstroke velocity by troglitazone was also significant at 1 microM. Voltage-clamp experiments revealed that troglitazone (10 microM) reversibly inhibited both the slow inward Ca2+ current and the steady-state K+ current. In contrast to troglitazone, pioglitazone (1-10 microM) had no significant effect on the excitability, action potential configuration, or membrane currents of myocytes. These results suggest that troglitazone, but not pioglitazone, modulates Na+, Ca2+ and K+ currents, leading to the changes in excitability and action potential configuration of ventricular myocytes.
Ikeda
S
S
Pharmaceutical Research Laboratories, Takeda Chemical Industries, Osaka, Japan. ikeda_shota@takeda.co.jp
Watanabe
T
T
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D000077205:Pioglitazone; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; D000077205:Pioglitazone