Antibody-mediated enhancement of calcium permeability in cardiac myocytes.
Our study shows that antibodies, specific to the ADP/ATP carrier of the inner mitochondrial membrane, crossreact with the cell surface of cardiac myocytes, where the calcium channel seems to be the antigenic determinant. The antibodies enhanced the calcium current and suppressed its inactivation. Affinity-purified antibodies (IgG) exhibit an acute cytotoxic effect, which required extracellular calcium and was prevented by calcium channel blockers. Our findings suggest that antibody-mediated cytotoxicity results secondary to calcium overload caused by enhanced cellular calcium permeability, requiring no complement-dependent process.
Schultheiss
H P
HP
Department of Internal Medicine, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
Kühl
U
U
Janda
I
I
Melzner
B
B
Ulrich
G
G
Morad
M
M
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001323:Autoantibodies / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004586:Electrophoresis; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008297:Male; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology*; D009206:Myocardium / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001323:Autoantibodies; D000226:Mitochondrial ADP, ATP Translocases; D009713:Nucleotidyltransferases; D002118:Calcium