Hong SJ, Liang HC, Shen CJ.Alteration of cyclopiazonic acid
(CPA) mediated contracture of mouse diaphragm after denervation.
Pharmacology. 2005 Mar;73(4):180-9
Department of Pharmacology, College of Medicine, National
Taiwan University, No.1, Sec.1, Jen-Ai Road, Taipei, Taiwan.
sjhong@ha.mc.ntu.edu.tw
As a major Ca(2+) source for muscle contraction, the
sarcoplasmic reticulum (SR) of skeletal muscle maintains its
Ca(2+) content by uptake of myoplasmic Ca(2+) and by
replenishment with extracellular Ca(2+). Since transection of
motor nerve alters the functions of SR Ca(2+) pump and
sarcolemma ion channels, this study explored the effect of
denervation on the contracture evoked by cyclopiazonic acid, an
inhibitor of SR Ca(2+) pump. In innervated hemidiaphragm,
cyclopiazonic acid (CPA) elicited a bimodal elevation of muscle
tone, which was dependent on extracellular Ca(2+) and
differentially inhibited by pretreatment with
2-aminoethoxydiphenylborane (APB) and U73122. Activation of
muscle Na(+) channels to simulate denervation-induced membrane
depolarization did not change the contracture profile. After
denervation for 5-14 days when the contracture induced by
caffeine was not yet depressed, cyclopiazonic acid (CPA)
elicited only APB-sensitive monophasic contracture. Stimulation
of ATP-regulated K(+) channels with lemakalim hyperpolarized
muscle membrane and attenuated cyclopiazonic acid (CPA)
contracture in denervated, but not innervated, hemidiaphragm.
The effects of lemakalim were antagonized by glybenclamide. It
is inferred that the bimodal cyclopiazonic acid (CPA)
contracture is resulted from distinct recruitments of Ca(2+)
entry and that denervation alters the voltage dependence and
down-regulates cyclopiazonic acid (CPA)-mediated Ca(2+) influx.
Copyright 2005 S. Karger AG, Basel.
PMID: 15604590
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