Nobuo Homma1,*, Gozoh Tsujimoto2 and Keitaro Hashimoto1
1Department of Pharmacology, Yamanashi Medical University, Shimokatoh-1110, Tamaho-cho, Yamanashi 409-3898, Japan
2Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, 3-35-31, Taishido, Setagaya-ku, Tokyo 154-8509, Japan
*Corresponding author. FAX: +81-552-73-6739, E-mail: nhomma@res.yamanashi-med.ac.jp
Abstract: The effects of bidisomide, an antiarrhythmic agent, on sodium current (INa) in isolated rat ventricular myocytes were investigated using a whole cell voltage clamp method. Bidisomide blocked INa with a Ki of 214 mM at a holding potential of -140 mV. The blockade of INa was enhanced at a less negative holding potential of -100 mV with a Ki of 21 mM. Bidisomide shifted the steady state inactivation curve to a negative potential direction by 20 mV without a significant change in the slope factor. Bidisomide slowed the time course of recovery of INa at a holding potential of -140 mV with a slow recovery phase. The time constant of recovery phase for bidisomide, disopyramide and mexiletine were 2703, 1858 and 757 ms, respectively. The development of the block of INa consisted of two phases in the presence of bidisomide. The fast and slow time constants were 11 and 648 ms. Bidisomide produced a use-dependent block of INa when the depolarizing pulse was repeated at 1 - 3 Hz. Our results indicate that bidisomide binds to rat cardiac sodium channels and that the dissociation kinetics of bidisomide from the inactivated sodium channel is slower than that of disopyramide.
Keywords: Bidisomide, Sodium current, Cardiac myocyte
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