Membrane action of ethmozin on normoxic and hypoxic canine Purkinje fibers.
Transmembrane potentials were recorded from canine Purkinje fiber preparations before and after perfusion with ethmozin (0.05, 0.2, and 1.0 microgram/ml). Under normal oxygenation (95% O2 + 5% CO2; n = 9), ethmozin at 0.05 microgram/ml significantly (p less than 0.05) reduced maximal rate of depolarization (MRD), from 750 +/- 61 to 709 +/- 58 V/s, without affecting other parameters. MRD was further decreased to 647 +/- 53 and 540 +/- 78 V/s at 0.2 and 1.0 microgram/ml of this agent. Reduction of maximal diastolic potential, from -86.1 +/- 6.0 to -84.6 +/- 5.9 mV, occurred only at 1.0 microgram/ml, suggesting that the decrease in MRD is not voltage dependent. Ethmozin significantly shortened the action potential duration at 50 (APD50) and 90% (APD90) repolarization, from 231 +/- 16 and 306 +/- 18 to 199 +/- 26 and 279 +/- 14 ms, respectively. At 1.0 microgram/ml, these values were further reduced. The effective refractory period also showed a concentration-dependent shortening, but the ratio of the refractory period to APD90 was increased. The membrane responsiveness curve was shifted by ethmozin to more negative potentials. The h infinity (inactivation of the fast Na+ current) curve was shifted by 3.8 mV to more negative values by 1.0 microgram/ml ethmozin. "Slow response" produced by high K+ + isoproterenol (0.025 microgram/ml) was not affected by ethmozin (1.0 and 5.0 microgram/ml). Ethmozin exaggerated the electrophysiologic effects of hypoxia (95% N2 + 5% CO2; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D016293:Moricizine; D010100:Oxygen / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D010640:Phenothiazines; D016293:Moricizine; D010100:Oxygen