title: Metabolic end products inhibit sarcoplasmic reticulum Ca2+ release and [3H]ryanodine binding.
abstract: Sarcoplasmic reticulum (SR) Ca2+ release channel function is modified by ligands (Mg2+, Ca2+, ATP, and H+) that are generated during a bout of exercise. We have examined the effects of changing intracellular metabolites on Ca2+ release, [3H]ryanodine binding, and single-Ca2+ release channel activity of SR isolated from white rabbit skeletal muscle. Increasing Mg2+ (from 0 to 4 mM) and decreasing pH (7.1-6.5) inhibited SR Ca2+ release and [3H]-ryanodine binding. In addition, increasing lactate concentrations from 2 to 20 mM inhibited [3H]ryanodine binding to SR vesicles, inhibited SR Ca2+ release, and decreased the single-channel open probability. These findings suggest that intracellular modifications that disrupt excitation-contraction coupling and decrease Ca2+ transients will promote a decline in tension development and contribute to muscle fatigue. In addition, we show that hydrogen peroxide induces Ca2+ release and increases [3H]ryanodine binding to its receptor, suggesting that reactive oxygen species produced during exercise may compromise muscle function by altering the normal gating of the SR Ca2+ release channel.
authors.affiliation: Department of Biology, University of Portland 97203, Oregon, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Favero
authors.forename: A C
authors.initials: AC
authors.lastname: Zable
authors.forename: M B
authors.initials: MB
authors.lastname: Bowman
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: J J
authors.initials: JJ
authors.lastname: Abramson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002132:Calcium Radioisotopes; D006859:Hydrogen / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008274:Magnesium / Q000378:metabolism; D018763:Muscle Fatigue / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012433:Ryanodine / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002132:Calcium Radioisotopes; D007773:Lactates; D017382:Reactive Oxygen Species; D012433:Ryanodine; D019344:Lactic Acid; D006859:Hydrogen; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium