title: Increased cardiomyocyte function and Ca2+ transients in mice during early congestive heart failure.
abstract: End-stage heart failure is believed to involve depressed cardiomyocyte contractility and Ca2+ transients. However, the time course of these alterations is poorly understood. We examined alterations in myocyte excitation-contraction coupling in a mouse model of early congestive heart failure (CHF) following myocardial infarction. One week after myocardial infarction was induced by ligation of the left coronary artery, CHF mice were selected based on established criteria (increased left atrial diameter, increased lung weight). Sham-operated animals (SHAM) served as controls. Echocardiographic measurements showed decreased global function in early CHF relative to SHAM, but increased local function in viable regions of the myocardium which deteriorated with time. Cardiomyocytes isolated from the non-infarcted septum also exhibited larger contractions in early CHF than SHAM (CHF=219.6+/-15.3% of SHAM values, P<0.05; 1 Hz field stimulation), and relaxation was more rapid (time to 50% relaxation=82.9+/-5.5% of SHAM values, P<0.05). Ca2+ transients (fluo-4 AM) were larger and decayed more rapidly in CHF than SHAM during both field stimulation (1 Hz) and voltage-clamp steps. Sarcoplasmic reticulum (SR) Ca2+ content was increased. Western blots showed that while SR Ca2+ ATPase (SERCA) expression was unaltered in CHF, phospholamban (PLB) was downregulated (60+/-11% of SHAM values, P<0.05). Thus, an increased SERCA/PLB ratio in CHF may promote SR Ca2+ re-uptake. Additionally, peak L-type Ca2+ current and Na+/Ca2+ exchanger expression were increased in CHF, suggesting increased sarcolemmal Ca2+ flux. Thus, in early CHF, alterations in Ca2+ homeostasis improve cardiomyocyte contractility which may compensate for loss of function in the infarction area.
authors.affiliation: Institute for Experimental Medical Research, Ullevaal University Hospital, Oslo, Norway. h.k.mork@medisin.uio.no
authors.forename: Halvor K
authors.initials: HK
authors.lastname: Mørk
authors.forename: Ivar
authors.initials: I
authors.lastname: Sjaastad
authors.forename: Jørn B
authors.initials: JB
authors.lastname: Sande
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: Ole M
authors.initials: OM
authors.lastname: Sejersted
authors.forename: William E
authors.initials: WE
authors.lastname: Louch
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013997:Time Factors; D000099211:Phospholamban
chemical_list: D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban