Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats

Howlett SE. Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats. Am J Physiol Heart Circ Physiol 298: H659-H670, 2010. First published December 4, 2009; doi:10.1152/ajpheart.00214.2009.-We evaluated effects of age on components of excitation-contraction (EC) coupling in ventricular myocytes from male and female rats to examine sex differences in mechanisms responsible for age-related contractile dysfunction. Myocytes were isolated from anesthetized young adult (similar to 3 mo) and aged (similar to 24 mo) Fischer 344 rats. Ca(2+) concentrations and contractions were measured simultaneously (37 degrees C, 2 Hz). Fractional shortening declined with age in males (6.7 +/- 0.6% to 2.4 +/- 0.4%; P < 0.05), as did peak Ca(2+) transients (47.7 +/- 4.6 to 28.1 +/- 2.1 nM; P < 0.05) and Ca(2+) current densities (-7.7 +/- 0.7 to -6.2 +/- 0.5 pA/pF; P < 0.05). Although sarcoplasmic reticulum (SR) Ca(2+) content was similar regardless of age in males, EC coupling gain declined significantly with age to 55.8 +/- 7.8% of values in younger males. In contrast with results in males, contraction and Ca(2+) transient amplitudes were unaffected by age in females. Ca(2+) current density declined with age in females (-7.5 +/- 0.5 to -5.1 +/- 0.7 pA/pF; P < 0.05), but SR Ca(2+) content actually increased dramatically (49.0 +/- 7.5 to 147.3 +/- 28.5 nM; P < 0.05). Even so, EC coupling gain was not affected by age in female myocytes. Age also promoted hypertrophy of male myocytes more than female myocytes. Age and sex differences in EC coupling were largely maintained when conditioning pulse frequency was increased to 4 Hz. Contractions, Ca(2+) transients, and EC coupling gain were also smaller in young females than in young males. Thus age-dependent changes are more prominent in myocytes from males than females. Increased SR Ca(2+) content may compensate for reduced Ca(2+) current to preserve contractile function in aged females, which may limit the detrimental effects of age on cardiac contractile function.