title: Myotoxin a reduces the threshold for calcium-induced calcium release in skeletal muscle.
abstract: Myotoxin a, isolated from the venom of the prairie rattlesnake Crotalus viridis viridis, induces necrosis in skeletal muscle. In isolated organelles, it has been reported that myotoxin a reduces Ca2+ uptake into the sarcoplasmic reticulum. The effects of the toxin on Ca2+ regulation were examined in heavy sarcoplasmic reticulum fractions from human and equine skeletal muscle. Ca2+ uptake and release (the threshold of Ca(2+)-induced Ca2+ release) were examined by dual wavelength spectrophotometry. The toxin lowered the threshold of Ca(2+)-induced Ca2+ release in a dose-dependent manner (1-10 microM) and this effect was antagonized by ruthenium red, a Ca2+ release channel blocker. Ca2+ uptake into equine heavy sarcoplasmic reticulum was not decreased by myotoxin a (10 microM) when Ca2+ release was blocked by ruthenium red. [3H]Ryanodine binding to equine heavy sarcoplasmic reticulum was converted from a relatively low affinity state to a higher affinity state by myotoxin a. These results suggest that the dominant effect of myotoxin a is to increase the Ca2+ sensitivity for the opening of the calcium release channel (ryanodine receptor). Myotoxin a may prove to be a useful tool to probe the modulation of calcium release in sarcoplasmic reticulum fractions.
authors.affiliation: Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102.
authors.forename: M L
authors.initials: ML
authors.lastname: Yudkowsky
authors.forename: J
authors.initials: J
authors.lastname: Beech
authors.forename: J E
authors.initials: JE
authors.lastname: Fletcher
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D003435:Crotalid Venoms / Q000633:toxicity*; D004347:Drug Interactions; D006736:Horses; D006801:Humans; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology*; D012433:Ryanodine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D003435:Crotalid Venoms; D012430:Ruthenium Red; D012433:Ryanodine; C018932:myotoxin A; D002118:Calcium