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Ca 2+ release induced by myotoxin a , a radio‐labellable probe having novel Ca 2+ release properties in sarcoplasmic reticulum
Author(s) -
Furukawa KenIchi,
Funayama Kaori,
Ohkura Masamichi,
Oshima Yoshiteru,
Tu Anthony T.,
Ohizumi Yasushi
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16199.x
Subject(s) - ruthenium red , caffeine , chemistry , endoplasmic reticulum , calcium , biophysics , biochemistry , biology , endocrinology , organic chemistry
1 Myotoxin a (MYTX), a polypeptide toxin purified from the venom of prairie rattlesnakes ( Crotalus viridis viridis ) induced Ca 2+ release from the heavy fraction (HSR) but not the light fraction of skeletal sarcoplasmic reticulum at concentrations higher than 1 μ m , followed by spontaneous Ca 2+ reuptake by measuring extravesicular Ca 2+ concentrations using the Ca 2+ electrode. 2 The rate of 45 Ca 2+ release from HSR vesicles was markedly accelerated by MYTX in a concentration‐dependent manner in the range of concentrations between 30 nM and 10 μ m , indicating the most potent Ca 2+ releaser in HSR. 3 The Ca 2+ dependency of MYTX‐induced 45 Ca 2+ release has a bell‐shaped profile but it was quite different from that of caffeine, an inducer of Ca 2+ ‐induced Ca 2+ release. 4 45 Ca 2+ release induced by MYTX was remarkable in the range of pCa between 8 and 3, whereas that by caffeine was prominent in the range of pCa, i.e., between 7 and 5.5. 5 MYTX‐induced 45 Ca 2+ release consists of both early and late components. The early component caused by MYTX at low concentrations (30–300 nM) completed within 20 s, while the late component induced by it at higher concentrations (>0.3μ m ) was maintained for at least 1 min. 6 Both the components were almost completely inhibited by inhibitors of Ca 2+ release such as Mg 2+ , ruthenium red and spermine. 7 45 Ca 2+ release induced by caffeine or β,γ‐methyleneadenosine 5′‐triphosphate (AMP‐PCP) was completely inhibited by high concentrations of procaine. Procaine abolished the early component but not the late one, suggesting that at least the early component is mediated through Ca 2+ ‐induced Ca 2+ release channels. 8 On the basis of these results, the character of Ca 2+ release induced by MYTX was quite different from that caused by caffeine or AMP‐PCP, suggesting that MYTX induces Ca 2+ release having novel properties in HSR. MYTX is the first polypeptide Ca 2+ inducer and has become a useful pharmacological tool for clarifying the mechanism of Ca 2+ release from skeletal muscle SR.