Liang HC, Shen CJ., Hong SJ
Dependence of cyclopiazonic-acid-induced muscle contractures on
extracellular Ca2+.
Can J Physiol Pharmacol. 2003 Dec;81(12):1101-9.
Department of Pharmacology, College of Medicine, National
Taiwan University, Taipei, Taiwan.
sjhong@ha.mc.ntu.edu.tw
Inhibition of Ca2+ uptake by the sarcoplasmic reticulum
decreases cytosolic Ca2+ clearance and also triggers Ca2+ influx
in response to Ca2+ store depletion. The role of extracellular
Ca2+ in the contractures evoked by cyclo-piazonic acid (CPA) and
thapsigargin (TG), Ca2+ pump inhibitors, was assessed in mouse
diaphragm. At 3-100 microM, CPA elicited a rapid-onset
contracture followed by a large elevation of muscle tone, which
corresponded temporally to the monophasic slow contracture
evoked by TG (1-30 microM). Irrespective of the differences in
profiles, contractures were prevented and inhibited by the
removal of extracellular Ca2+, but not by nicardipine and
SK&F96365, blockers of voltage-gated (L-type) and
receptor-operated Ca2+ channels. Mn2+ and Ni2+ preferentially
depressed the fast-phase contracture, whereas long-term
pretreatment with LY294002, U73122, and
2-aminoethoxydiphenylborance, inhibitors of phosphatidylinositol
kinase, phospholipase C, and inositol trisphosphate receptors,
suppressed the slow-phase contracture. When contracture was
inhibited, the twitch response remained augmented and prolonged
by CPA and TG, indicating that the inhibition was not due to
malfunction of the contractile apparatus. For preparations
incubated in Ca2+-free medium containing CPA, a monophasic fast
upstroke of muscle tone developed as extracellular Ca2+ was
restored. The results suggest that the bimodal contracture
induced by CPA is mediated by the recruitment of distinct Mn2+-
and U73122-sensitive Ca2+ entries. The ongoing two-component
Ca2+ entries might merge if the muscle preparation was
preconditioned with CPA in Ca2+-free medium to deplete cellular
Ca2+ stores.
PMID: 14719028
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