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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Suzuki, R. Kodama, I. Toyama, J. Maruyama, K. |
| Description | Author Affiliation: Kodama I ( Department of Circulation, Nagoya University, Japan.) |
| Abstract | 1. The effects of SD-3212 on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, SD-3212 > or = 3 microM caused a significant decrease in the maximum upstroke velocity (Vmax) of action potential without affecting resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 3. In the presence of SD-3212, trains of stimuli at rates > or = 0.5 Hz led to a use-dependent inhibition of Vmax. The time constant for the recovery of Vmax from the use-dependent block was 1.3 s. 4. Voltage-dependence of Vmax inhibition by SD-3212 was investigated in single myocytes. The curves relating membrane potential and Vmax were shifted by SD-3212 (10 microM) in a hyperpolarizing direction by 6.2 mV. 5. In myocytes treated with SD-3212 (10 microM), the Vmax of test action potentials preceded by conditioning clamp to 0 mV was decreased progressively as the clamp pulse duration was prolonged. Vmax of test action potentials following a long (1 s) 0 mV clamp recovered at a time constant ranging from 1.01 to 1.22 s, being shorter at the more negative potential within a range from -70 to -90 mV. 6. These findings suggest that the primary electrophysiological effect of SD-3212 is a use- and voltage-dependent inhibition of sodium channels. From the onset and offset kinetics of the use-dependent block, SD-3212 is located between fast and intermediate kinetic Class-I drugs. From the state-dependence of sodium channel block, SD-3212 belongs to inactivated channel blockers. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 114 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1995-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Anti-Arrhythmia Agents Pharmacology Heart Drug Effects Thiazoles Vasodilator Agents Action Potentials Animals Electric Stimulation Electrophysiology Guinea Pigs Heart Ventricles Cytology In Vitro Techniques Kinetics Membrane Potentials Myocardium Papillary Muscles Patch-Clamp Techniques |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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