title: Lactate inhibits Ca(2+) -activated Ca(2+)-channel activity from skeletal muscle sarcoplasmic reticulum.
abstract: Sarcoplasmic reticulum (SR) Ca(2+)-release channel function is modified by ligands that are generated during about of exercise. We have examined the effects of lactate on Ca(2+)- and caffeine-stimulated Ca2+ release, [3H]ryanodine binding, and single Ca(2+)-release channel activity of SR isolated from rabbit white skeletal muscle. Lactate, at concentrations from 10 to 30 mM, inhibited Ca(2+)- and caffeine-stimulated nodine binding to and inhibited Ca(2+)- and caffeine-stimulated [3H]ryanodine binding to and inhibited Ca(2+)- and caffeine-stimulated Ca2+ release from SR vesicles. Lactate also inhibited caffeine activation of single-channel activity in bilayer reconstitution experiments. These findings suggest that intense muscle activity, which generates high concentrations of lactate, will disrupt excitation-contraction coupling. This may lead to decreases in Ca2+ transients promoting a decline in tension development and contribute to muscle fatigue.
authors.affiliation: Department of Biology, University of Portland, Oregon 97203, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Favero
authors.forename: A C
authors.initials: AC
authors.lastname: Zable
authors.forename: D
authors.initials: D
authors.lastname: Colter
authors.forename: J J
authors.initials: JJ
authors.lastname: Abramson
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007773:Lactates / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D007773:Lactates; D002118:Calcium