E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions

1 Muscle Biology Laboratory, Texas A&M University, College Station, Texas 77843-4243; and 2 Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute, Blacksburg, Virginia 24061-0430 The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (P o ) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice ( n = 164) were injured in vivo with 150 eccentric contractions. P o , caffeine-, 4-chloro- m -cresol-, and K + -induced contracture forces, sarcoplasmic reticulum (SR) Ca 2+ release and uptake rates, and intracellular Ca 2+ concentration ([Ca 2+ ] i ) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in P o (~51%) compared with caffeine-induced force (~11-21%), we estimate that E-C coupling failure can explain 57-75% of the P o decrement from 0 to 5 days postinjury. Comparable reductions in P o and K + -induced force (51%), and minor reductions (0-6%) in the maximal SR Ca 2+ release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca 2+ ] i was elevated and peak tetanic [Ca 2+ ] i was reduced, whereas peak 4-chloro- m -cresol-induced [Ca 2+ ] i was unchanged immediately after injury. By 3 days postinjury, 4-chloro- m -cresol-induced [Ca 2+ ] i became depressed, probably because of decreased SR Ca 2+ release and uptake rates (17-31%). These data indicate that the decrease in P o during the first several days after injury primarily stems from a failure in the E-C coupling process. excitation-contraction; extensor digitorum longus; fluo 3; fura red; calcium-selective minielectrode