title: SUN 1165: a new antiarrhythmic Na current blocker in ventricular myocytes of guinea-pig.
abstract: 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 (Vmax) in a concentration dependent manner (IC30 = 1.7 X 10(-5) M) more markedly (about six times) than the contractile force. 3. In single ventricular cells, the Na current (INa) was reduced by the drug in a concentration dependent manner (IC30 = 9.1 X 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 INa from inactivation was prolonged by SUN 1165. 6. The Ca current (ICa) was also blocked by the drug in a concentration dependent manner but much less than INa (IC30 = 5.5 X 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.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D008012:Lidocaine; D012964:Sodium; C042288:pilsicainide