As a major Ca2+ source for muscle contraction, the sarcoplasmic reticulum (SR) of skeletal muscle maintains its Ca2+ content by uptake of myoplasmic Ca2+ and by replenishment with extracellular Ca2+. Since transection of motor nerve alters the functions of SR Ca2+ pump and sarcolemma ion channels, this study explored the effect of denervation on the contracture evoked by cyclopiazonic acid (CPA), an inhibitor of SR Ca2+ pump. In innervated hemidiaphragm, CPA elicited a bimodal elevation of muscle tone, which was dependent on extracellular Ca2+ 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, CPA elicited only APB-sensitive monophasic contracture. Stimulation of ATP-regulated K+ channels with lemakalim hyperpolarized muscle membrane and attenuated CPA contracture in denervated, but not innervated, hemidiaphragm. The effects of lemakalim were antagonized by glybenclamide. It is inferred that the bimodal CPA contracture is resulted from distinct recruitments of Ca2+ entry and that denervation alters the voltage dependence and down-regulates CPA-mediated Ca2+ influx.

Keywords:
ATP-regulated K+ channel, K+ channel opener, Skeletal muscle, Store-operated Ca2+ entry, Sarcoplasmic reticulum, 2-Aminoethoxydiphenylborane
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© 2005 S. Karger AG, Basel
2005
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