ISSN:
1423-0127
Keywords:
SK&F 96365
;
Crotamine
;
Calcium channel blocker
;
Local anesthetic
;
Sodium channel
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract The effects of SK&F 96365, a blocker of the receptor-operated Ca2+ channel, on contractilities and the Na+ channel of mouse diaphragm were studied. SK&F 96365 (10–50 µM) reversibly inhibited twitches, tetanic contractions and muscle and nerve action potentials. The IC50 was 17–24 µM. 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 IC50 to about 4 µM. 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 of excitable membranes at a concentration range that inhibits the receptor-operated calcium channel.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02253347
