Altered Ca 2+ sparks and gating properties of ryanodine receptors in aging cardiomyocytes

Abstract

To investigate the cellular mechanisms for altered cardiac function in senescence, we measured Ca 2+ transients and Ca 2+ sparks in ventricular cardiomyocytes from 6- to 24-month-old Fisher 344 (F344) rat hearts. The single channel properties of ryanodine receptors from adult and senescent hearts were also studied. In senescent myocytes, we observed a decreased peak [Ca 2+] i amplitude and an increased time constant for decay ( τ), both of which correlated with a reduced Ca 2+ content of the sarcoplasmic reticulum (SR). Our studies also revealed that senescent cardiomyocytes had an increased frequency of Ca 2+ sparks and a slight but statistically significant decrease in average amplitude, full-width-at-half-maximum (FWHM) and full-duration-at-half-maximum (FDHM). Single channel recordings of ryanodine receptors (RyR2) demonstrated that in aging hearts, the open probability ( P o) of RyR2 was increased but the mean open time was shorter, providing a molecular correlate for the increased frequency of Ca 2+ sparks and decreased size of sparks, respectively. Thus, modifications of normal RyR2 gating properties may play a role in the altered Ca 2+ homeostasis observed in senescent myocytes.