Altered Ca2+ sparks and gating properties of ryanodine receptors in aging cardiomyocytes

Cell Calcium. 2005 Jun;37(6):583-91. doi: 10.1016/j.ceca.2005.03.002. Epub 2005 Apr 7.

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 (tau), 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Animals
  • Calcium / metabolism*
  • In Vitro Techniques
  • Ion Channel Gating*
  • Myocytes, Cardiac / metabolism*
  • Rats
  • Rats, Inbred F344
  • Ryanodine Receptor Calcium Release Channel / metabolism*

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Calcium