title: Alteration of cyclopiazonic acid-mediated contracture of mouse diaphragm after denervation.
abstract: 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 (CPA), an inhibitor of SR Ca(2+) pump. In innervated hemidiaphragm, 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, 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 Ca(2+) entry and that denervation alters the voltage dependence and down-regulates CPA-mediated Ca(2+) influx.
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, No.1, Sec.1, Jen-Ai Road, Taipei, Taiwan. sjhong@ha.mc.ntu.edu.tw
authors.forename: S J
authors.initials: SJ
authors.lastname: Hong
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Liang
authors.forename: Ching-Jung
authors.initials: CJ
authors.lastname: Shen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001681:Biological Assay / Q000379:methods; D001896:Boron Compounds / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D019806:Cromakalim / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation / Q000379:methods; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009121:Muscle Denervation / Q000379:methods; D009529:Nicardipine / Q000494:pharmacology; D010791:Phrenic Nerve / Q000503:physiopathology / Q000601:surgery; D011760:Pyrrolidinones / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology
chemical_list: D001896:Boron Compounds; D003435:Crotalid Venoms; D004963:Estrenes; D007211:Indoles; D011760:Pyrrolidinones; D019806:Cromakalim; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002110:Caffeine; D009529:Nicardipine; C109986:2-aminoethoxydiphenyl borate; C010563:crotamine; D005905:Glyburide; C000543:cyclopiazonic acid