Abstract 2337: Male-Specific Changes in Myocyte Size and Calcium Channel Expression in Old Age
Aging is the single largest risk factor for the development of cardiac dysfunction. Cardiac contractile function becomes slowed in old age associating with myofilament modification and age-dependent changes in intracellular calcium regulation. These changes however appear to differ between genders. This study examined differences in intracellular calcium regulation and cardiac myocyte structure between young male (YM) and young female (YF) C57BL6 mice at 6 months of age, and old male (OM) and old female (OF) mice at 24 months of age. We assessed the hypothesis that age-dependent changes would be exaggerated in males compared with females associating with gender-specific changes in intracellular calcium regulation. Mice of either gender at 24 months were significantly heavier than young mice (YF: 21.8±0.7 g, YM: 29.2±1.2 g, vs. OF 32.6±0.9 g and OM 36.7±2.4 g (means±S.D.); p<0.05, n=18, 21, 25 and 8 respectively), but all groups possessed a similar heart to body weight ratio (average 8.4±0.4). Male mice had significant myocyte hypertrophy in terms of width and length in old age (Width: OM: 27.5±1.2 μM vs. YM 15.2±0.9 μM) - an effect not observed in the female mice. Assessment of calcium currents using whole cell patch clamp (4 mM external Ca2+) showed peak calcium current density elicited by pulses from −100 mV to 0 mV did not differ significantly between genders or age groups (average 6.8±0.3 pA/pF). However analysis of current-voltage profiles revealed a significant amount of a low-voltage activated current present in OM but not OF, YM or YF mice (current amplitude 0.9±0.2 pA/pF at −40mV), which possessed the characteristics of a T-type calcium current shown by abolishment of the current using a holding potential of −60 mv or low concentrations of nickel (50 μM). Western blot revealed a 2.5±0.5 fold increase in T-type channel protein expression in OM compared with YM mice. No significant changes in T-type channel expression were found in female mice.
In conclusion only male mice show myocyte hypertrophy in old age accompanied by an increase in expression of the T-type calcium channel, this be may a signal for adaptation and/or an adaptation altering intracellular calcium kinetics in old age, resulting in altered contractile function and arrhythmia susceptibility.