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

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 (similar to 7 mo) and aged (similar to 24 mo) male and female mice. Intracellular Ca2+ concentrations and unloaded cell shortening were measured at 37 degrees 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.