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

Abstract

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) Ca²⁺release and uptake rates, and intracellular Ca²⁺ concentration ([Ca²⁺]_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 Ca²⁺ 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 [Ca²⁺]_iwas elevated and peak tetanic [Ca²⁺]_iwas reduced, whereas peak 4-chloro-m-cresol-induced [Ca²⁺]_iwas unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca²⁺]_ibecame depressed, probably because of decreased SR Ca²⁺ 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.