Sarcoplasmic reticulum Ca²⁺ release declines in muscle fibers from aging mice

¹ Wake Forest Univ Sch Med

^* To whom correspondence should be addressed. E-mail: odelbono{at}wfubmc.edu.

Submitted on August 1, 2007
Revised on September 4, 2007
Accepted on 3 December 2007

	Abstract

This study hypothesized that decline in 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 (FDB) muscle. Significant differences in tetanic but not 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'-tetra-acetic acid (EGTA, 20mM). 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 ECC, but not in maximal SR-releasable Ca²⁺, account for the age-dependent decline in intracellular Ca²⁺ mobilization and specific force.

Key Words: aging, calcium, fluorescence, sarcoplasmic reticulum, skeletal muscle