Effects of elevated extracellular potassium concentrations on the class III antiarrhythmic action of sotalol.
The electrophysiological and mechanical effects of sotalol, a beta-adrenergic blocker with Class III antiarrhythmic properties, were compared with those of atenolol in rabbit right ventricular papillary muscles studied in vitro using intracellular microelectrodes. Sotalol produced a dose-dependent increase in action potential duration and effective refractory period without any effect on parameters of rapid inward current. Atenolol had no Class I or Class III effect. The actions of equipotent beta-blocking concentrations of sotalol (10(-4) mol X litre-1) and of atenolol (10(-5) mol X litre-1) in elevated extracellular potassium concentrations of 8 and 12 mmol X litre-1 were investigated. There were reductions in membrane potential, action potential amplitude and upstroke velocity in elevated potassium which were not influenced by sotalol and atenolol, apart from a small additional depression of action potential amplitude and membrane potential in 12 mmol X litre-1 potassium. Hyperkalaemia caused shortening in action potential duration but lengthening in effective refractory period (post-repolarisation refractoriness). The increase in effective refractory period over control produced by sotalol in normal potassium was preserved in elevated potassium. This effect was attributable to lengthening of action potential duration rather than alteration in the duration of post-repolarisation refractoriness. The Class III effects of sotalol are preserved even in partially depolarised fibres where rapid inward current is depressed.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D001262:Atenolol; D013015:Sotalol; D007545:Isoproterenol; D011188:Potassium