title: Altered Ca2+ 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 (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.
authors.affiliation: Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Zhu
authors.forename: Beth A
authors.initials: BA
authors.lastname: Altschafl
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Héctor H
authors.initials: HH
authors.lastname: Valdivia
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schmidt
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium