Ca2+ release induced by myotoxin a, a radio‐labellable probe having novel Ca2+ release properties in sarcoplasmic reticulum

Ken‐Ichi ‐I Furukawa, Kaori Funayama, Masamichi Ohkura, Yoshiteru Oshima, Anthony T. Tu, Yasushi Ohizumi

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Myotoxin a (MYTX), a polypeptide toxin purified from the venom of prairie rattlesnakes (Crotalus viridis viridis) induced Ca2+ release from the heavy fraction (HSR) but not the light fraction of skeletal sarcoplasmic reticulum at concentrations higher than 1 μm, followed by spontaneous Ca2+ reuptake by measuring extravesicular Ca2+ concentrations using the Ca2+ electrode. The rate of 45Ca2+ release from HSR vesicles was markedly accelerated by MYTX in a concentration‐dependent manner in the range of concentrations between 30 nM and 10 μm, indicating the most potent Ca2+ releaser in HSR. The Ca2+ dependency of MYTX‐induced 45Ca2+ release has a bell‐shaped profile but it was quite different from that of caffeine, an inducer of Ca2+‐induced Ca2+ release. 45Ca2+ 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. MYTX‐induced 45Ca2+ 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 (>0.3μm) was maintained for at least 1 min. Both the components were almost completely inhibited by inhibitors of Ca2+ release such as Mg2+, ruthenium red and spermine. 45Ca2+ 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 Ca2+‐induced Ca2+ release channels. On the basis of these results, the character of Ca2+ release induced by MYTX was quite different from that caused by caffeine or AMP‐PCP, suggesting that MYTX induces Ca2+ release having novel properties in HSR. MYTX is the first polypeptide Ca2+ inducer and has become a useful pharmacological tool for clarifying the mechanism of Ca2+ release from skeletal muscle SR. 1994 British Pharmacological Society

Original languageEnglish
Pages (from-to)233-239
Number of pages7
JournalBritish Journal of Pharmacology
Volume113
Issue number1
DOIs
Publication statusPublished - 1994 Sep

Keywords

  • Ca release
  • Myotoxin a
  • caffeine
  • excitation‐contraction coupling
  • procaine
  • sarcoplasmic reticulum
  • skeletal muscle

ASJC Scopus subject areas

  • Pharmacology

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