T. Maeno et al., EFFECTS OF INHIBITORS OF OUABAIN-SENSITIVE NA-ATPASE AND LI+ IONS ON THE NEUROMUSCULAR-TRANSMISSION OF THE FROG(,K+), Japanese Journal of Physiology, 45(3), 1995, pp. 397-410
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.