title: Abnormal myocyte Ca2+ homeostasis in rabbits with pacing-induced heart failure.
abstract: To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca2+ concentration ([Ca2+]i) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca2+ current (ICa,L) and Na+/Ca2+ exchanger current (INa/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]i with the use of sodium-binding benzofuran isophthalate (SBFI) and fluo 3 in ventricular myocytes isolated from control and paced rabbits. The peak systolic and diastolic levels and the amplitude of electrically stimulated [Ca2+]i transients (0.25 Hz, extracellular Ca2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca2+]i transients. ICa,L density was markedly decreased in PF myocytes. INa/Ca at -40 mV elicited by rapid exposure to 0 Na+ solution with a rapid solution switcher was significantly reduced in PF myocytes, suggesting that the function of the Na+/Ca2+ exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca2+]i transient when the Na+/Ca2+ exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca2+-ATPase function. RNase protection assay showed decreased levels of Na+/Ca2+ exchanger and SR Ca2+-ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca2+ channels, Na+/Ca2+ exchanger, and SR Ca2+-ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca2+]i transients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed.
authors.affiliation: Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
authors.forename: A
authors.initials: A
authors.lastname: Yao
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: A
authors.initials: A
authors.lastname: Nonaka
authors.forename: I
authors.initials: I
authors.lastname: Zubair
authors.forename: K W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: J H
authors.initials: JH
authors.lastname: Bridge
authors.forename: G
authors.initials: G
authors.lastname: Muelheims
authors.forename: J
authors.initials: J
authors.lastname: Ross
authors.forename: W H
authors.initials: WH
authors.lastname: Barry
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006706:Homeostasis; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D010138:Pacemaker, Artificial; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium