title: Potentiation by metal ions of ryanodine contracture of the mouse diaphragm.
abstract: The aim of this study was to elucidate the possible mechanism of the potentiating action of metal ions (Cu2+, Hg2+, Ag+ and SeO3(2-)) on the ryanodine-induced contracture of the mouse diaphragm. The ryanodine contracture in the quiescent muscle could be augmented by either electrical stimulation or pretreatment with high K+ of the diaphragm. Lowering the external Ca2+ concentration from 2.5 mM to 1 microM or the addition of 7 microM d-tubocurarine, which abolished the muscle excitability by blocking the receptors of acetylcholine, markedly attenuated the ryanodine contracture. Application of Cu2+, Hg2+, Ag+ and SeO3(2-) but not Ni2+ and Co2+, to quiescent muscle restored the ryanodine contracture. The potentiating effects of Hg2+, Ag+ and high K+ were dependent on the presence of external Ca2+ (2.5 mM) and intact transverse tubular systems but the effects of Cu2+ and SeO3(2-) were not. Treatment with 1 mM dithiothreitol 10 min after the application of metal ions and then subsequent addition of ryanodine abolished the potentiating effects of Hg2+ and Ag+ but not those of Cu2+ and SeO3(2-). Although ryanodine by itself had no effect on 45Ca2+ uptake by the mouse diaphragm, it significantly potentiated the increased 45Ca2+ uptake elicited by Cu2+ and Hg2+. Further elucidation of the interaction between metal ions and ryanodine on the outer sarcolemma showed that all of these metal ions, including the inactive Co2+ and Ni2+, not only decreased the membrane potential but also altered the membrane input resistance, effects which were not correlated with the potentiating effects of the metal ions on the ryanodine contracture.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei.
authors.forename: S H
authors.initials: SH
authors.lastname: Liu
authors.forename: S Y
authors.initials: SY
authors.lastname: Lin-Shiau
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002132:Calcium Radioisotopes; D003964:Diaphragm / Q000187:drug effects*; D004229:Dithiothreitol / Q000494:pharmacology; D004357:Drug Synergism; D004558:Electric Stimulation; D005260:Female; D005990:Glycerol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008670:Metals / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D002132:Calcium Radioisotopes; D008670:Metals; D012433:Ryanodine; D002110:Caffeine; D005990:Glycerol; D002118:Calcium; D004229:Dithiothreitol; D014403:Tubocurarine