On the mechanism of the different sensitivity of Purkinje and myocardial fibers to strophanthidin.
The mechanism of the different sensitivity of Purkinje and myocardial fibers to strophanthidin was studied in these tissues isolated from the same hearts. Membrane potentials, force and, in some experiments, intracellular sodium activity were recorded under conditions that vary the sodium load in the absence and presence of strophanthidin. Strophanthidin (0.1-0.3 microM) increased force in percent terms more and at a faster rate in Purkinje than in myocardial fibers. Tetrodotoxin (TTX, 2 microM) markedly reduced whereas high [Na]o (176.6 mM) and veratridine (0.2 microM) potentiated strophanthidin inotropy in Purkinje but not in myocardial fibers. The rate of force development was augmented by high [Na]o and veratridine in Purkinje fibers but in myocardial fibers this effect was absent with high [Na]o and smaller with veratridine. Strophanthidin increased the action potential duration at plateau level in Purkinje and decreased it in myocardial fibers. The effects of TTX, high [Na]o and veratridine on the action potential were more pronounced in Purkinje than in myocardial fibers. TTX decreased far more and adding strophanthidin increased intracellular sodium activity (aiNa) less in Purkinje fibers. Strophanthidin increased aiNa to a similar extent in the presence of high [Na]o and veratridine in the two tissues. Thus, changes in Na influx modify the action potential duration, force and strophanthidin inotropy more in Purkinje than in myocardial fibers. This greater sensitivity of Purkinje fibers to strophanthidin does not appear to be related to a larger increase in aiNa, but rather to the changes in action potential (and consequent changes in calcium influx).
Iacono
G
G
Department of Physiology, State University of New York, Health Science Center, Brooklyn.
Vassalle
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D012964:Sodium / Q000378:metabolism; D013327:Strophanthidin / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D013779:Tetrodotoxin; D013327:Strophanthidin; D014701:Veratridine; D012964:Sodium; D002118:Calcium