Effects of mexiletine on transmembrane action potentials as affected by external potassium concentration and by rate of stimulation in guinea-pig papillary muscles.
1. The effects of mexiletine and quinidine were compared on transmembrane potentials in guinea-pig papillary muscles, using conventional microelectrode techniques. 2. Mexiletine (23.1 mumol/l) decreased the maximum rate of rise of the action potential (Vmax) and increased the ratio of the effective refractory period to the action potential duration at 90% repolarization level (ERP/APD90); these effects were prominent with elevation of the external potassium concentration ([K]o) from 2.7 to 5.4, 8.1 and 10.0 mmol/l. 3. The percentage decrease in Vmax induced by 5 and 10 mumol/l of quinidine was approximately constant in 2.7, 5.4 and 10.0 mmol/l [K]o solutions. 4. The decrease in Vmax produced by mexiletine was progressively increased as the driving rate was raised from 0.25 to 5Hz. This rate-dependent change was pronounced when the concentration was raised from 23.1 to 46.2 and 92.4 mumol/l. 5. Mexiletine in concentrations of 23.1 and 92.4 mumol/l delayed the recovery of Vmax in a premature action potential to the level of Vmax in the conditioning action potentials at the driving rate of 0.25 Hz. 6. It appears that mexiletine exerts its anti-arrhythmic action by a selective depressant effect on depolarized cells (high [K]0) and cells with high frequency discharges, as is the case with lignocaine.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology
D011437:Propylamines; D008801:Mexiletine; D011802:Quinidine; D011188:Potassium