Role of Ca2+, membrane excitability, and Ca2+ stores in failing muscle contraction with aging

• Published in: Experimental gerontology Vol. 44; no. 4; pp. 261 - 273
• Main Authors: Payne, Anthony Michael, Jimenez-Moreno, Ramón, Wang, Zhong-Ming, Messi, María Laura, Delbono, Osvaldo
• Format: Journal Article
• Language: English
• Published: England 01-04-2009
• Subjects: Animals; Calcium - metabolism; Calcium Signaling - physiology; Ion Channel Gating - physiology; Ions - metabolism; Membranes - metabolism; Mice; Muscle Contraction - physiology; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - physiology
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2008.09.013

Excitation-contraction (EC) coupling in a population of skeletal muscle fibers of aged mice becomes dependent on the presence of external Ca(2+) ions (Payne, A.M., Zheng, Z., Gonzalez, E., Wang, Z.M., Messi, M.L., Delbono, O., 2004b. External Ca(2+)-dependent excitation - contraction coupling in a population of aging mouse skeletal muscle fibers. J. Physiol. 560, 137-155.). However, the mechanism(s) underlying this process remain unknown. In this work, we examined the role of (1) extracellular Ca(2+); (2) voltage-induced influx of external Ca(2+) ions; (3) sarcoplasmic reticulum (SR) Ca(2+) depletion during repeated contractions; (4) store-operated Ca(2+) entry (SOCE); (5) SR ultrastructure; (6) SR subdomain localization of the ryanodine receptor; and (7) sarcolemmal excitability in muscle force decline with aging. These experiments show that external Ca(2+), but not Ca(2+) influx, is needed to maintain force upon repetitive fiber electrical stimulation. Decline in fiber force is associated with depressed SR Ca(2+) release. SR Ca(2+) depletion, SOCE, and the putative segregated Ca(2+) release store do not play a significant role in external Ca(2+)-dependent contraction. More importantly, a significant number of action potentials fail in senescent mouse muscle fibers subjected to a stimulation frequency. These results indicate that failure to generate action potentials accounts for decreased intracellular Ca(2+) mobilization and tetanic force in aging muscle exposed to a Ca(2+)-free medium.