title: Cardiac contractile dysfunction in J2N-k cardiomyopathic hamsters is associated with impaired SR function and regulation.
abstract: Although dilated cardiomyopathy (DCM) is known to result in cardiac contractile dysfunction, the underlying mechanisms are unclear. The sarcoplasmic reticulum (SR) is the main regulator of intracellular Ca2+ required for cardiac contraction and relaxation. We therefore hypothesized that abnormalities in both SR function and regulation will contribute to cardiac contractile dysfunction of the J2N-k cardiomyopathic hamster, an appropriate model of DCM. Echocardiographic assessment indicated contractile dysfunction, because the ejection fraction, fractional shortening, cardiac output, and heart rate were all significantly reduced in J2N-k hamsters compared with controls. Depressed cardiac function was associated with decreased cardiac SR Ca2+ uptake in the cardiomyopathic hamsters. Reduced SR Ca2+ uptake could be further linked to a decrease in the expression of the SR Ca(2+)-ATPase and cAMP-dependent protein kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16. Depressed PLB phosphorylation was paralleled with a reduction in the activity of SR-associated PKA, as well as an elevation in protein phosphatase activity in J2N-k hamster. The results of this study suggest that an alteration in SR function and its regulation contribute to cardiac contractile dysfunction in the J2N-k cardiomyopathic hamster.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada R2H 2A6.
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Babick
authors.forename: Elliott J F
authors.initials: EJ
authors.lastname: Cantor
authors.forename: John T
authors.initials: JT
authors.lastname: Babick
authors.forename: Nobuakira
authors.initials: N
authors.lastname: Takeda
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
authors.forename: Thomas
authors.initials: T
authors.lastname: Netticadan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D004562:Electrocardiography; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology; D010766:Phosphorylation; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D017868:Cyclic AMP-Dependent Protein Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban