title: Intraluminal Ca2+ dependence of Ca2+ and ryanodine-mediated regulation of skeletal muscle sarcoplasmic reticulum Ca2+ release.
abstract: The action of ryanodine upon sarcoplasmic reticulum (SR) Ca2+ handling is controversial with evidence for both activation and inhibition of SR Ca2+ release. In this study, the role of the intraluminal SR Ca2+ load was probed as a potential regulator of ryanodine-mediated effects upon SR Ca2+ release. Through dual-wavelength spectroscopy of Ca2+:antipyrylazo III difference absorbance, the intraluminal Ca2+ dependence of ryanodine and Ca(2+)-induced Ca2+ release (CICR) from skeletal SR vesicles was examined. Ryanodine addition after initiation of Ca2+ uptake (a) increased the intraluminal Ca2+ sensitivity of CICR and (b) stimulated spontaneous Ca2+ release with a delayed onset. These ryanodine effects were inversely proportional to the intraluminal Ca2+ load. Ryanodine also inhibited subsequent CICR after reaccumulation of Ca2+ released from the initial CICR. These results provide evidence that ryanodine inhibits transitions between low and high affinity Ca2+ binding states of an intraluminal Ca2+ compartment, possibly calsequestrin. Conformational transitions of calsequestrin may be reciprocally coupled to transitions between open and closed states of the Ca2+ release channel.
authors.affiliation: Faculty of Graduate Studies, University of British Columbia, Vancouver, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Gilchrist
authors.forename: A N
authors.initials: AN
authors.lastname: Belcastro
authors.forename: S
authors.initials: S
authors.lastname: Katz
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D006706:Homeostasis; D007700:Kinetics; D009132:Muscles / Q000378:metabolism*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D012433:Ryanodine; D000255:Adenosine Triphosphate; D002118:Calcium