title: Cardiac dysfunction in murine autoimmune myocarditis.
abstract: We have investigated the pathophysiological basis of cardiac dysfunction in autoimmune myocarditis and in the resulting dilated cardiomyopathy. To this end we utilized the myosin-induced autoimmune myocarditis model in BALB/c mice. Myocarditis has been found to be associated with massive ventricular lymphocyte infiltration and a 50% reduction in tail artery blood flow, reflecting the depressed cardiac function in myocarditis. Action potential characteristics of control and diseased isolated ventricular myocytes were (mean+/-SEM): resting potential: -68.1+/-1. 1,-68.3+/-0.7 mV; action potential amplitude: 96.5+/-10.4, 92.3+/-4. 4 mV; action potential duration at 80% repolarization (APD80) 38+/-5, 116+/-24* ms; * P<0.05. We utilized the whole cell voltage clamp technique to explore ion currents involved in APD prolongation and arrhythmogenic activity, and found that in diseased myocytes the transient outward current (Ito) was markedly attenuated. At a membrane potential of +40 mV, in control and in diseased myocytes, I(to) current density was 14.7+/-1.5 and 6.5+/-1.4 pA/pF, respectively, P<0.005. In contrast, the L-type Ca2+current (ICa,L) remained unchanged. To further explore the basis for cardiac impairment, we simultaneously measured [Ca2+]i transient and contraction in isolated normal and diseased myocytes. The major findings indicated that both the relaxation kinetics of [Ca2+]i transients and myocyte contraction were significantly faster in the diseased myocytes. In conclusion, substantial, potentially reversible, electrophysiological and mechanical perturbations in ventricular myocytes from mice with myosin-induced autoimmune myocarditis appear to contribute to disease-related cardiac dysfunction.
authors.affiliation: Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Minerva Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, 31096, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Less
authors.forename: M
authors.initials: M
authors.lastname: Shilkrut
authors.forename: I
authors.initials: I
authors.lastname: Rubinstein
authors.forename: G
authors.initials: G
authors.lastname: Berke
authors.forename: O
authors.initials: O
authors.lastname: Binah
mesh_terms: D000200:Action Potentials; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D020013:Calcium Signaling; D002311:Cardiomyopathy, Dilated / Q000209:etiology; D002478:Cells, Cultured; D004553:Electric Conductivity; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000166:cytology; D009218:Myosins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D001324:Autoantigens; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D009218:Myosins