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Sarcoplasmic Reticulum Ca²⁺ Release Declines in Muscle Fibers from Aging Mice

Ramón Jiménez-Moreno ^*, Zhong-Min Wang ^*, Robert C. Gerring ^* and Osvaldo Delbono ^*  

^* Department of Physiology and Pharmacology, Department of Internal Medicine, Section on Gerontology, and Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Correspondence: Address reprint requests to Osvaldo Delbono, Dept. of Physiology and Pharmacology, Wake Forest University School of Medicine, 1 Medical Center Blvd., Winston-Salem, NC 27157. Tel.: 336-716-9802; Fax: 336-716-2273; E-mail: odelbono{at}wfubmc.edu.

This study hypothesized that decline in sarcoplasmic reticulum (SR) Ca²⁺ release and maximal SR-releasable Ca²⁺ 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 Ca²⁺ in response to 4-CmC did not differ significantly. SR Ca²⁺ release was recorded in whole-cell patch-clamped fibers in the linescan mode of confocal microscopy using a low-affinity Ca²⁺ indicator (Oregon green bapta-5N) with high-intracellular ethylene glycol-bis(-aminoethyl ether)-N,N,N'N'-tetraacetic acid (20 mM). Maximal SR Ca²⁺ 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 Ca²⁺ release in fibers from old compared to young mice. Voltage-dependent inactivation of SR Ca²⁺ 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 Ca²⁺, account for the age-dependent decline in intracellular Ca²⁺ mobilization and specific force.