title: Sarcoplasmic reticulum function in murine ventricular myocytes overexpressing SR CaATPase.
abstract: To examine the effects of the overexpression of sarcoplasmic reticulum (SR) CaATPase on function of the SR and Ca2+ homeostasis, we measured [Ca2+]i transients (fluo-3), and L-type Ca2+ currents (ICa.L), Na/Ca exchanger currents (INa/Ca), and SR Ca2+ content with voltage clamp in ventricular myocytes isolated from wild type (WT) mice and transgenic (SRTG) mice. The amplitude of [Ca2+]i transients was insignificantly increased in SRTG myocytes, while the diastolic [Ca2+]i tended to be lower. The initial and terminal declines of [Ca2+]i transients were significantly accelerated in SRTG myocytes, implying a functional upregulation of the SR CaATPase. We examined the functional contribution of only the SR CaATPase to the initial and the terminal phase of the decline of [Ca2+]i, by abruptly inhibiting Na/Ca exchange with a rapid switcher device. The rate of [Ca2+] decline mediated by the SR CaATPase was increased by 40% in SRTG compared with WT myocytes. The function of the L-type Ca2+ channel was unchanged in SRTG myocytes, while INa/Ca density was slightly (10%) decreased. Measured SR Ca2+ content was significantly increased by 29% in SRTG myocytes. Thus, overexpression of SR CaATPase markedly accelerates the decline of [Ca2+]i transients, and induces in increase in SR Ca2+ content, with some downregulation of the Na/Ca exchanger.
authors.affiliation: Division of Cardiology, University of Utah Health Science Center, Salt Lake City 84132, USA.
authors.forename: A
authors.initials: A
authors.lastname: Yao
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: W H
authors.initials: WH
authors.lastname: Dillmann
authors.forename: W H
authors.initials: WH
authors.lastname: Barry
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000502:physiology; D013997:Time Factors