EFFECTS OF INHIBITORS OF OUABAIN-SENSITIVE NA-ATPASE AND LI+ IONS ON THE NEUROMUSCULAR-TRANSMISSION OF THE FROG(,K+)

The effect of blockade of ouabain-sensitive alpha 2 and alpha 3 (neura l type) isozymes of Na+,K+-ATPase was investigated on frog neuromuscul ar preparations by recording the frequency augmentation-potentiation ( FAP) of the endplate potential, an electrophysiological and neuropharm acological technique to analyze the drug actions on the release proces s of the readily releasable transmitter quanta. Erythrosin B, which wa s thought to selectively inhibit the neural type Na+,K+-ATPase, pivote d the log-linear FAP relation counterclockwise without altering the in tercept on the ordinate. Chlormadinone had a similar action. An increa se in the concentration of extracellular K+ ions pivoted the FAP relat ion 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 l eaving its slope unchanged. Cinnarizine, a blocker for inositol-1,4,5- trisphosphate-induced Ca2+ release, and ,2-bis(2-aminophenoxy)ethane-N ,N,N',N'-tetraacetic acid, a specific intracellular Ca2+ chelator, sig nificantly antagonized the potentiating action of Li+. The ouabain-sen sitive neural type Na+,K+-ATPase isozyme, which is abundant in neural tissues, seems to play an important role in stimulation frequency-depe ndent modulation of the quantal transmitter release such as FAP.