Inhibition of the Sodium Channel by SK&F 96365, an Inhibitor of the Receptor-Operated Calcium Channel, in Mouse Diaphragm.
The effects of SK&F 96365, a blocker of the receptor-operated Ca(2+) channel, on contractilities and the Na(+) channel of mouse diaphragm were studied. SK&F 96365 (10-50 &mgr;M) reversibly inhibited twitches, tetanic contractions and muscle and nerve action potentials. The IC(50) was 17-24 &mgr;M. The inward Na(+) current was suppressed and its recovery from inactivations delayed. Crotamine, a peptide toxin that binds to neurotoxin receptor site 3 of the muscle Na(+) channel, enhanced the inhibitory effects of SK&F 96365 and reduced the IC(50) to about 4 &mgr;M. Veratridine had similar effects, although it was less effective than crotamine. On the other hand, the crotamine-induced membrane depolarizations and spontaneous discharges of muscle action potentials were inhibited by SK&F 96365 noncompetitively. The inhibitory effects of tetrodotoxin and tetracaine were additive with those of SK&F 96365 but were enhanced slightly by crotamine. The results suggested that SK&F 96365 acts on a distinct site and blocks the Na(+) channel fo excitable membranes at a concentration range that inhibits the receptor-operated calcium channel. Copyright 1994 S. Karger AG, Basel
Hong
S.J.
SJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan (ROC).
Lin
W.-W.
WW
Chang
C.C.
CC