Effects of inhibitors of ouabain-sensitive Na+, K(+)-ATPase and Li+ ions on the neuromuscular transmission of the frog.
The effect of blockade of ouabain-sensitive alpha 2 and alpha 3 (neural type) isozymes of Na+, K(+)-ATPase was investigated on frog neuromuscular preparations by recording the frequency augmentation-potentiation (FAP) of the endplate potential, an electrophysiological and neuropharmacological technique to analyze the drug actions on the release process of the readily releasable transmitter quanta. Erythrosin B, which was thought to selectively inhibit the neural type Na+, K(+)-ATPase, pivoted the log-linear FAP relation counterclockwise without altering the intercept on the ordinate. Chlormadinone had a similar action. An increase in the concentration of extracellular K+ ions pivoted the FAP relation clockwise with a concomitant upward shift of the intercept on the ordinate, and low K+ Ringer's solution produced an inverse effect. In contrast, Li+ ions shifted the FAP relation upwards dose-dependently leaving its slope unchanged. Cinnarizine, a blocker for inositol-1,4,5-trisphosphate-induced Ca2+ release, and 5,5'-dimethyl-1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid, a specific intracellular Ca2+ chelator, significantly antagonized the potentiating action of Li+. The ouabain-sensitive neural type Na+, K(+)-ATPase isozyme, which is abundant in neural tissues, seems to play an important role in stimulation frequency-dependent modulation of the quantal transmitter release such as FAP.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D004923:Erythrosine / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D010042:Ouabain; D008094:Lithium; D000254:Sodium-Potassium-Exchanging ATPase; D004923:Erythrosine; D011188:Potassium