E-C COUPLING FAILURE IN MOUSE EDL MUSCLE AFTER IN-VIVO ECCENTRIC CONTRACTIONS

The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maxi mal isometric tetanic force (P-o) in mouse extensor digitorum longus ( EDL) muscles after eccentric contractions and to elucidate possible me chanisms. 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) Ca2+ release and uptake rates, and intracellular Ca2+ c oncentration ([Ca2+](i)) were then measured in vitro in injured and co ntralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in P-o (similar t o 51%) compared with caffeine-induced force (similar to 11-21%), we es timate that E-C coupling failure can explain 57-75% of the P-o decreme nt from 0 to 5 days postinjury. Comparable reductions in P-o and K+-in duced force (51%), and minor reductions (0-6%) in the maximal SR Ca2release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser sca nning microscopy indicated that resting [Ca2+](i) was elevated and pea k tetanic [Ca2+](i) was reduced, where as peak 4-chloro-m-cresol-induc ed [Ca2+](i) was unchanged immediately after injury. By 3 days postinj ury, 4-chloro-m-cresol-induced [Ca2+](i) became depressed, probably be cause of decreased SR Ca2+ release and uptake rates (17-31%). These da ta indicate that the decrease in P-o during the first several days aft er injury primarily stems from a failure in the E-C coupling process.