Sarcoplasmic Reticulum Ca^sup 2+^ Release Declines in Muscle Fibers from Aging Mice

• Published in: Biophysical journal Vol. 94; no. 8; p. 3178
• Main Authors: Jiménez-Moreno, Ramón, Wang, Zhong-Min, Gerring, Robert C, Delbono, Osvaldo
• Format: Journal Article
• Language: English
• Published: New York Biophysical Society 15-04-2008
• Subjects: Aging; Calcium; Cells; Fibers; Rodents
• ISSN: 0006-3495; 1542-0086

This study hypothesized that decline in sarcoplasmic reticulum (SR) Ca^sup 2+^ release and maximal SR-releasable Ca^sup 2+^ contributes to decreased specific force with aging. To test it, we recorded electrically evoked maximal isometric specific force followed by 4-chloro-m-cresol (4-CmC)-evoked maximal contracture force in single intact fibers from the mouse flexor digitorum brevis muscle. Significant differences in tetanic, but not in 4-CmC-evoked, contracture forces were recorded in fibers from aging mice as compared to younger mice. Peak intracellular Ca^sup 2+^ in response to 4-CmC did not differ significantly. SR Ca^sup 2+^ release was recorded in whole-cell patch-clamped fibers in the linescan mode of confocal microscopy using a low-affinity Ca^sup 2+^ indicator (Oregon green bapta-5N) with high-intracellular ethylene glycol-bis(α-aminoethyl ether)-N,N,N',N'-tetraacetic acid (20 mM). Maximal SR Ca^sup 2+^ release, but not voltage dependence, was significantly changed in fibers from old compared to young mice. Increasing the duration of fiber depolarization did not increase the maximal rate of SR Ca^sup 2+^ release in fibers from old compared to young mice. Voltage-dependent inactivation of SR Ca^sup 2+^ release did not differ significantly between fibers from young and old mice. These findings indicate that alterations in excitation-contraction coupling, but not in maximal SR-releasable Ca^sup 2+^, account for the age-dependent decline in intracellular Ca^sup 2+^ mobilization and specific force. [PUBLICATION ABSTRACT]