Akera T, Ku D D, Frank M, Brody T M, Iwasa J
J Pharmacol Exp Ther. 1976 Oct;199(1):247-54.
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.
通过用灰黄霉素I（GTX）对抗钠泵的作用，研究了跨膜钠转运改变与心肌收缩性之间的关系。GTX是一种先前已证明可增加静息钠内流的药物。在高达0.1 mM的浓度下，GTX在体外未能影响Na +，K + - 三磷酸腺苷酶活性。在豚鼠心脏的电驱动左心房制备物中，1 μM GTX产生轻微的去极化，并似乎降低动作电位的上升速度，GTX（0.1 - 1 μM）也产生正性肌力作用，该作用在20分钟内逐渐显现。在更高浓度下，GTX会产生心律失常。在存在10 μM普萘洛尔的情况下也观察到了GTX的这些作用。药物洗脱后，GTX的正性肌力和心律失常作用是可逆的。GTX的这些作用也被河豚毒素逆转，河豚毒素已被证明可抵消GTX对钠通透性的影响。这些数据与跨膜钠转运改变影响心肌收缩性的假设一致。
