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

This study hypothesized that decline in sarcoplasmic reticulum (SR) Ca(2+) release and maximal SR-releasable Ca(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(2+) in response to 4-CmC did not differ significantly. SR Ca(2+) release was recorded in whole-cell patch-clamped fibers in the linescan mode of confocal microscopy using a low-affinity Ca(2+) indicator (Oregon green bapta-5N) with high-intracellular ethylene glycol-bis(alpha-aminoethyl ether)-N,N,N'N'-tetraacetic acid (20 mM). Maximal SR Ca(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(2+) release in fibers from old compared to young mice. Voltage-dependent inactivation of SR Ca(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(2+), account for the age-dependent decline in intracellular Ca(2+) mobilization and specific force.