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1 Pharmacology, Dalhousie University, Halifax, Canada
* To whom correspondence should be addressed. E-mail: susan.howlett{at}dal.ca.
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 months) and aged (~24 months) 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 to 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 and cardiac EC-coupling.
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