The modulation of Ca2+ release by a cardiotoxin (CTX) from Naja naja kaouthia snake venom was examined in terminal cisternae-containing fractions from equine and human skeletal muscle. Pretreatment with CTX (10 microM) decreased by 27% (human muscle), or had no effect on (equine muscle), the threshold of Ca(2+)-induced Ca2+ release. If terminal cisternae fractions were first preloaded with Ca2+ to greater than 65% of the threshold of Ca(2+)-induced Ca2+ release and then CTX added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of CTX after a Ca2+ preload of less than 60% of the threshold of Ca(2+)-induced Ca2+ release did not elicit Ca2+ release in preparations from either species. Ruthenium red (10 microM) antagonized CTX-induced Ca2+ release, whereas dantrolene (10 microM) did not. These findings suggest that the effects of CTX on the Ca2+ release channel are dependent on Ca2+ preload and that CTX may be an important probe of the Ca(2+)-modulated Ca2+ release process and in understanding regulation of Ca2+ release in skeletal muscle from different species.
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