Mechanism of grayanotoxin III-induced afterpotentials in feline cardiac Purkinje fibers.
Grayanotoxins are known to produce cardiac tachyarrhythmias. It is unknown, however, which of three mechanisms, i.e., reentry, induction of automatic activity or induction of triggered activity, accounts for grayanotoxin-induced arrhythmias. To distinguish between these possible mechanisms, effects of grayanotoxin III (GTX III) on the electrical activity of isolated feline cardiac Purkinje fibers were examined under control conditions in which reentry was not likely to occur (perfusion with an oxygenated physiological saline solution at 30 degrees C and pH 7.4) and under several other conditions known to either enhance or block triggered activity. GTX III alone (1 microM) produced either 1-2 low amplitude or repetitive, suprathreshold after potentials within 15 min of administration. At the onset of GTX III-induced afterpotentials, the configuration of electrically driven action potentials was only slightly altered. Increasing stimulation frequency, raising extracellular calcium concentration or lowering extracellular potassium concentration, each of which augment triggered activity, enhanced the production of GTX III-induced afterpotentials. Furthermore, verapamil, raising extracellular potassium concentration or phenytoin, each of which block triggered activity, suppressed afterpotentials elicited by GTX III. These results indicate that the mechanism underlying grayanotoxin-induced arrhythmias is the production of triggered activity in the form of oscillatory afterpotentials.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002415:Cats; D004224:Diterpenes / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D004224:Diterpenes; D010672:Phenytoin; D014700:Verapamil; D011188:Potassium; D002118:Calcium; C020751:grayanotoxin III