Increased contractility and altered Ca(2+) transients of mouse heart myocytes conditionally expressing PKCbeta.
Activation of protein kinase C (PKC) in heart muscle signals hypertrophy and may also directly affect contractile function. We tested this idea using a transgenic (TG) mouse model in which conditionally expressed PKCbeta was turned on at 10 wk of age and remained on for either 6 or 10 mo. Compared with controls, TG cardiac myocytes demonstrated an increase in the peak amplitude of the Ca(2+) transient, an increase in the extent and rate of shortening, and an increase in the rate of relengthening at both 6 and 10 mo of age. Phospholamban phosphorylation and Ca(2+)-uptake rates of sarcoplasmic reticulum vesicles were the same in TG and control heart preparations. At 10 mo, TG skinned fiber bundles demonstrated the same sensitivity to Ca(2+) as controls, but maximum tension was depressed and there was increased myofilament protein phosphorylation. Our results differ from studies in which PKCbeta was constitutively overexpressed in the heart and in studies that reported a depression of myocyte contraction with no change in the Ca(2+) transient.
Huang
L
L
Department of Physiology and Biophysics, Program in Cardiovascular Sciences, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Wolska
B M
BM
Montgomery
D E
DE
Burkart
E M
EM
Buttrick
P M
PM
Solaro
R J
RJ
D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000254:growth & development / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D007527:Isoenzymes; D010710:Phosphates; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D000099211:Phospholamban