Abstract 1452: Myocyte Aging Conditions Cell Growth and Contractile Function
The recognition that the heart can replace old dying myocytes by activation of resident cardiac stem cells raises the possibility that organism, organ and cell age do not coincide and that the myocardium is composed of a heterogeneous population of parenchymal cells. Cardiomyocytes differ in size and shape, suggesting that differentiating, adult and senescent cells with different mechanical properties coexist and sustain ventricular function. Therefore, left ventricular myocytes were isolated from adult mice and their contractile, electrical and calcium transients characteristics were analyzed in cells of different volume. These parameters were evaluated in terms of the expression of the senescent-associated protein p16INK4a and telomeric length. Mono-, bi- and multi-nucleated myocytes constituted 5%, 92%, and 3% of the population, respectively. Myocytes varied in volume from 2,000 to 95,000 μm3, and myocyte size correlated positively with the number of nuclei in the cells. Similarly, 5%, 19% and 34% of mono-, bi- and multi-nucleated myocytes were positive for p16INK4a, respectively. Conversely, myocyte volume was inversely related to telomere length with a 4.3 kbp decrease in telomeric length per 10,000 um3 of myocyte volume. Cell aging was coupled with a decrease in sarcomere shortening, 8.5% per 10,000 um3, which was paralleled by a decrease in calcium transients amplitude, 10% per 10,000 um3. Sarcoplasmic reticulum calcium load and ICaL density were independent variables of cellular aging. Calcium transients elicited by depolarizing steps to different potentials or of variable duration did not vary among myocytes, suggesting that cell volume does not affect calcium-induced calcium-release. Importantly, the increase in volume was coupled with a faster repolarizing phase of the action potential that conditions the availability of this cation for the initiation of myocyte shortening. In conclusion, myocyte aging results in a decline in developed calcium and myocyte performance, which are mediated by a reduction in calcium entry through a decrease in the duration of the action potential. These observations suggest that calcium, which is essential for cell growth and contraction, is cycled differently in cells of different volume and age.