Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum

Terence G. Favero 1 , 2 , Anthony C. Zable 2 , David Colter 1 , and Jonathan J. Abramson 2 1 Department of Biology, University of Portland, Portland, Oregon 97203; and 2 Department of Physics, Portland State University, Portland, Oregon 97207 Received 6 June 1996; accepted in final form 3 October 1996. Favero, Terence G., Anthony C. Zable, David Colter, and Jonathan J. Abramson. Lactate inhibits Ca 2+ -activated Ca 2+ -channel activity from skeletal muscle sarcoplasmic reticulum. J. Appl. Physiol. 82(2): 447-452, 1997. 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 Ca 2+ release, [ 3 H]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 [ 3 H]ryanodine binding to and inhibited Ca 2+ - and caffeine-stimulated Ca 2+ 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 Ca 2+ transients promoting a decline in tension development and contribute to muscle fatigue. calcium; muscle fatigue; caffeine; lactate; skeletal muscle 0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society