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  • Title: Effects of grayanotoxin I on cardiac Na + K + -adenosine triphosphatase activity, transmembrane potential and myocardial contractile force.
    Author: Akera T, Ku DD, Frank M, Brody TM, Iwasa J.
    Journal: J Pharmacol Exp Ther; 1976 Oct; 199(1):247-54. PubMed ID: 135836.
    Abstract:
    The relationship between altered transmembrane sodium movements and myocardial contractility was studied by opposing the action of the sodium pump with grayanotoxin I (GTX), an agent previously shown to increase resting sodium influx. GTX failed to affect Na+,K+-adenosine triphosphatase activity in vitro in concentrations as high as 0.1 mM. In electrically driven left atrial preparations of guinea-pig hearts, 1 mugM GTX produced a slight depolarization and appeared to decrease the upstroke velocity of the action potential, GTX (0.1-1 mugM) also produced a positive inotropic effect which developed over a 20-minute period. At higher concentrations, GTX produced arrhythmias. These effects of GTX were also observed in the presence of 10 mugM propranolol. Positive inotropic and arrhythmic effects of GTX were reversible after washout of the drug. These effects of GTX were also reversed by tetrodotoxin, an agent which has been shown to counteract the effect of GTX on sodium permeability. These data are consistent with a hypothesis that altered transmembrane sodium movement effects myocardial contractility.
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