Activation of Ca-permeable cation channels by myocarditis-associated antibody in guinea pig ventricular myocytes.
The pathogenesis of myocarditis and dilated cardiomyopathy is though to involve autoimmunological processes and myocardial calcium overload. Serum containing antiheart antibodies associated with a murine model of myocarditis increased [Ca2+]i in guinea pig ventricular myocytes only in the presence of extracellular Ca2+. The antiheart antibody-positive serum activated Ca(2+)-permeable cation channels that were insensitive to dihydropyridines and membrane stretch. The permeability sequence was Ba2+ > Ca2+ > Na+ approximately K+, and the single-channel conductance to Ba2+ was 12 pS. The channel was activated by extracellular application of the serum during on-cell recording, which suggests that a soluble intracellular messenger may be involved. The antibody-positive serum did not alter voltage-gated Ca2+ currents. We propose that excess Ca entry in myocarditis and dilated cardiomyopathy results from activation of a Ca(2+)-permeable cationic channel by the autoantibodies.
Tominaga
M
M
Third Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Matsumori
A
A
Horie
M
M
Yoshida
H
H
Okada
Y
Y
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D016257:Fura-2; D006168:Guinea Pigs; D006352:Heart Ventricles; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000097:blood / Q000276:immunology*; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D002412:Cations; D007473:Ion Channels; D001464:Barium; D002118:Calcium; D016257:Fura-2