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

• Published in: British journal of pharmacology Vol. 136; no. 6; pp. 803 - 810
• Main Authors: Arikawa, Masaya, Takahashi, Naohiko, Kira, Tetsuya, Hara, Masahide, Saikawa, Tetsunori, Sakata, Toshiie
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-2002
• Subjects: Animals; Calcium; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - physiology; Cells, Cultured; Chromans - pharmacology; diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; electrophysiology; Heart Ventricles - cytology; Heart Ventricles - drug effects; Hypoglycemic Agents - pharmacology; Male; myocytes; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Patch-Clamp Techniques; Rats; Rats, Wistar; Thiazoles - pharmacology; Thiazolidinediones; Troglitazone
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704757

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 (ICa,L) in cardiac myocytes, which may underlie its cardioprotective effects. However, inhibition by troglitazone of ICa,L in diabetic cardiac myocytes has not been characterized.
Using whole‐cell voltage‐clamp techniques, ICa,L was measured in ventricular myocytes isolated from 4–6 weeks streptozotocin (STZ)‐induced diabetic rats and age‐matched control rats.
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 ICa,L.
Troglitazone decreased amplitude of ICa,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 μmol l−1, respectively.
Troglitazone at 5 μmol l−1 did not significantly influence the voltage dependency of steady‐state inactivation or the inactivation time course of ICa,L in either control or diabetic myocytes.
Since troglitazone inhibits ICa,L more effectively in STZ‐induced diabetic ventricular myocytes, this agent may prevent cardiac dysfunction in diabetes.
British Journal of Pharmacology (2002) 136, 803–810. doi:10.1038/sj.bjp.0704757