title: Studies on contractures induced in mouse diaphragm by caffeine and cupric and selenite ions.
abstract: Mouse diaphragm contractures induced by Cu2+, caffeine and selenite were studied comparatively. Both Cu2+- and caffeine-contractures were produced rapidly and relaxed spontaneously; the selenite-contracture occurred after a latent period of about 45 min and lasted for more than 3 hr. All contractures were myogenic, since neither d-tubocurarine nor tetrodotoxin prevented them. The susceptibility of these contractures to the depletion and replenishment of Ca2+ differed: the Cu2+-contracture increased proportionally with rising extracellular Ca2+ concentrations ranging from 2.5 to 12.5 mM and were abolished by 5 mM EGTA. Caffeine- and selenite-contractures were not affected by changes in extracellular Ca2+ concentration. The caffeine-contracture was abolished by EGTA in high concentration (30 mM) and the selenite-contracture was inhibited by 50 mM EGTA. After removal of Ca2+ with 5 mM EGTA, followed by replacement with 2.5 mM Ca2+ for 1 min, the Cu2(+)-contracture was fully restored. Caffeine- and selenite-contractures were restored only after a longer period (10-20 min) of re-exposure to Ca2+. These findings suggest that the Cu2(+)-contracture is dependent on external Ca2+ and probably caused by an increasing Ca2+ entry through sarcolemma. Caffeine- and selenite-contractures apparently result from internal Ca2+ release by sarcoplasmic reticulum. Substitution of either Sr2+ or Co2+ for Ca2+ fully supports the Cu2(+)-contracture. 45Ca2+ uptake and calcium content of the diaphragm were markedly increased by Cu2+ but not by selenite. Furthermore, the Cu2(+)-contracture was inhibited by exposing the outer membrane to trypsin, phospholipase C or saponin. The selenite-contracture was inhibited only by trypsin. The caffeine-contracture was unaffected by these treatments. These results support the notion that the Cu2(+)-contracture is induced by an increased entry of Ca2+ through the outer membrane. Cu2(+)-, caffeine- and selenite-contractures were respectively abolished, potentiated and unaffected by chronic denervation of the diaphragm. This and the other findings provide evidence that Cu2(+)-, caffeine- and selenite-contractures are induced in mouse diaphragm muscle via different sites of action.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, R.O.C.
authors.forename: S Y
authors.initials: SY
authors.lastname: Lin-Shiau
authors.forename: W M
authors.initials: WM
authors.lastname: Fu
authors.forename: S H
authors.initials: SH
authors.lastname: Liu
authors.forename: C T
authors.initials: CT
authors.lastname: Ni
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D010791:Phrenic Nerve / Q000187:drug effects; D012132:Respiratory Muscles / Q000378:metabolism* / Q000502:physiology; D020887:Selenious Acid; D012643:Selenium / Q000494:pharmacology*; D013324:Strontium / Q000494:pharmacology
chemical_list: D003035:Cobalt; D002110:Caffeine; D004533:Egtazic Acid; D003300:Copper; D020887:Selenious Acid; D012643:Selenium; D002118:Calcium; D013324:Strontium