Effects of immunoglobulin G from patients with dilated cardiomyopathy on rat cardiomyocytes.
This study was designed to compare the effects of purified antibodies against the beta(1)-adrenoceptor autoantibodies and total immunoglobulin G obtained during immunoadsorption on L-type Ca(2+) currents, action potentials and cell shortening, in rat ventricular myocytes. Patients with dilated cardiomyopathy frequently develop autoantibodies against beta(1)-adrenoceptors, which can be removed by immunoadsorption. There is some controversy, however, whether the beneficial effects of this therapeutic option are due to the removal of cardiostimulatory or cardiodepressive antibodies. Therefore we studied the effects of immunoglobulin G on two of the regulators of excitation-contraction coupling and on cell shortening. Immunoglobulin G was obtained during immunoadsorption therapy. Dissociated myocytes from rat hearts were electrically stimulated and cell shortening was measured by cell edge detection. Single electrode patch clamp technique in current or voltage clamp mode was used to measure L-type Ca(2+) currents or action potentials, respectively. (-)-Isoprenaline was used for comparative purposes. In comparison to (-)-isoprenaline, immunoglobulin G increased Ca(2+) current to a similar extent, but prolonged the plateau duration of action potentials to a lesser extent. Immunoglobulin G and beta(1)-adrenoceptor enhanced cell shortening to a similar degree, however, the effects were smaller than with (-)-isoprenaline. The increase in contraction amplitude was prevented by (-)-bisoprolol. We conclude that both beta(1)-adrenoceptors and immunoglobulin G derived from patients positive for beta(1)-adrenoceptor autoantibodies mediate the cardiostimulatory effects via beta(1)-adrenoceptors.
Christ
Torsten
T
Department of Pharmacology and Toxicology, Medical Faculty, Dresden University of Technology, D-01309 Dresden, Germany. christ@rcs.urz.tu-dresden.de
Adolph
Esther
E
Schindelhauer
Stefan
S
Wettwer
Erich
E
Dobrev
Dobromir
D
Wallukat
Gerd
G
Ravens
Ursula
U
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D048429:Cell Size / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology
D000318:Adrenergic beta-Agonists; D001323:Autoantibodies; D020746:Calcium Channels, L-Type; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1; D007545:Isoproterenol; D002118:Calcium