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Cardiac excitation-contraction coupling is altered in myocytes from aged male mice but not in cells from aged female mice

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada

Submitted 17 January 2006 ; accepted in final form 19 May 2006

This study characterized age-related alterations in excitation-contraction (EC)-coupling in ventricular myocytes and investigated whether these alterations are affected by the sex of the animal. Voltage-clamp experiments were conducted in myocytes from young adult (7 mo) and aged (24 mo) male and female mice. Intracellular Ca²⁺ concentrations and unloaded cell shortening were measured at 37°C with fura-2 and a video edge detector. Fractional shortening and Ca²⁺ current density were significantly reduced in aged male myocytes compared with those in young adult male cells. In addition, Ca²⁺ transients were significantly smaller in aged male myocytes. Sarcoplasmic reticulum (SR) content, assessed by rapid application of 10 mM caffeine, declined with age in male myocytes. However, EC coupling gain and fractional release of SR Ca²⁺ were similar in young adult and aged male cells. In contrast to results in male animals, fractional shortening and Ca²⁺ current densities were similar in young adult and aged myocytes isolated from female hearts. Furthermore, Ca²⁺ transient amplitudes were unaffected by age in female cells. Interestingly, SR Ca²⁺ content was elevated in aged female myocytes, and fractional SR Ca²⁺ release declined with age in females. However, the gain of EC coupling was not different in myocytes from young adult and aged female mice. These data demonstrate that age-related alterations in EC coupling are more prominent in myocytes from male hearts than in cells from female hearts and suggest that it is important to consider sex as a variable in studies of the effects of aging on cardiac EC coupling.

senescence; sex; sarcoplasmic reticulum; calcium transients; calcium-induced calcium release.

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