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 maximal isometric tetanic force (Po) 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. Po, 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 Po (approximately 51%) compared with caffeine-induced force (approximately 11-21%), we estimate that E-C coupling failure can explain 57-75% of the Po decrement from 0 to 5 days postinjury. Comparable reductions in Po 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+]i was elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol-induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease in Po during the first several days after injury primarily stems from a failure in the E-C coupling process.
Ingalls
C P
CP
Muscle Biology Laboratory, Texas A&M University, College Station, Texas 77843-4243, USA. Ingalls@unix.tamu.edu
Warren
G L
GL
Williams
J H
JH
Ward
C W
CW
Armstrong
R B
RB
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013268:Stimulation, Chemical
D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D011188:Potassium; D002118:Calcium