Sun 1165: A new antiarrhythmic na current blocker in ventricular myocytes of guinea-pig

• Published in: Comparative biochemistry and physiology. C, Comparative pharmacology Vol. 87; no. 2; pp. 237 - 243
• Main Authors: Inomata, Norio, Ishihara, Takafumi, Akaike, Norio
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 1987; New York, NY Pergamon Press
• Subjects: Action Potentials - drug effects; Animals; Antiarythmic agents; Biological and medical sciences; Cardiovascular system; Dose-Response Relationship, Drug; Guinea Pigs; Heart - drug effects; Ion Channels - metabolism; Kinetics; Lidocaine - analogs & derivatives; Lidocaine - pharmacology; Male; Medical sciences; Myocardial Contraction - drug effects; Myocardium - metabolism; Pharmacology. Drug treatments; Sodium - metabolism; Heart; Calcium; Papillary muscle; Rodentia; Electrophysiology; Action potential; Heart ventricle; Ionic channel; Contraction; Myocyte; Vertebrata; Mammalia; Guinea pig; Sodium; Animal; Circulatory system; Mechanism of action; Antiarrhythmia agent
• ISSN: 0306-4492; 0742-8413
• DOI: 10.1016/0742-8413(87)90003-X

1. We compared the effect of a new antiarrhythmic compound, SUN 1165, on Na and Ca channels in papillary muscles and enzymatically dispersed single ventricular cells of guinea-pig. Action potential and contractile force in papillary muscle were measured by the conventional microelectrode technique and a strain gauge. The membrane currents were measured in internally perfused and voltage clamped cells by a single suction pipette technique. 2. In papillary muscles, SUN 1165 depressed the maximum rate of rise of action potential ( V max) in a concentration dependent manner (IC 30= 1.7 × 10 −5 M) more markedly (about six times) than the contractile force. 3. In single ventricular cells, the Na current ( I Na) was reduced by the drug in a concentration dependent manner ( IC 30 = 9.1 × 10 −6 M) . 4. It showed frequency-dependent block and the steady-state inactivation curve was shifted to more negative potentials. 5. The recovery of I Na from inactivation was prolonged by SUN 1165. 6. The Ca current ( I Ca) was also blocked by the drug in a concentration dependent manner but much less than I Na ( IC 30 = 5.5 × 10 −5 M) . 7. These results suggested that SUN 1165 causes a selective inhibition of Na channels in guinea-pig ventricular cells at the antiarrhythmic concentrations.