I K+ (2.4-15.6mmoll-') antagonized the positive inotropic effect of dihydro-ouabain. The concentration-effect curves became steeper with the shift to higher concentrations of the glycoside. At 1.2 mmol 1-Ca2+, an increase in K+ from 2.4 to 12 mmol 1-P' required tenfold higher concentrations of dihydro-ouabain to produce equal inotropic effects. This factor was reduced to four at 3.2 mmol I-, Ca2+ . The same change in K+ concentration, at 1.2 mmol 1-' Ca2+, diminished the inotropic effect of ouabain on rested-state contractions by a factor of six. 2 The positive inotropic effect of Ca2+ was also antagonized by K+ (1.2-12 mmol 1-'). Reduction of Na+ from 140 to 70 mmol 1-' abolished the antagonistic action of K+ (1.2-8.0 mmol 1-'). Moreover the inotropic effect of Ca2" was enhanced.3 Reduction of Na+, from 140 to 70 mmol -', antagonized the positive inotropic effect of dihydroouabain more at low (2.4 mmol l') than at high (8.0 mmol I') K+. Accordingly, the extent of the dihydro-ouabain-K+ antagonism was reduced. 4 When the K+ concentration was increased from 2.4 to 12mmoll-', [3H]-ouabain binding was reduced by a factor of three. This is less than the reduction in the inotropic effectiveness of ouabain or dihydro-ouabain. 5 Reduction of stimulation frequency from 1 to 0.1215 Hz did not significantly alter the antagonistic effect of K+. Diminution of Vmax of the action potential was observed only at K+ concentrations greater than 5.9 mmol 1-, whereas the resting membrane potential was continuously depolarized over the entire range of K+ concentrations. 6 The results support the view that the reduction in receptor affinity cannot be the sole cause of the antagonism between the glycoside and K+. Impairment of passive Na+ influx during diastole, due to the K+-dependent depolarization of the resting membrane potential, contributed to about one half of the glycoside-K+ antagonism.
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