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Effects of immunoglobulin G from patients with dilated cardiomyopathy on rat cardiomyocytes

Item Type:Article
Title:Effects of immunoglobulin G from patients with dilated cardiomyopathy on rat cardiomyocytes
Creators Name:Christ, T. and Adolph, E. and Schindelhauer, S. and Wettwer, E. and Dobrev, D. and Wallukat, G. and Ravens, U.
Abstract:This study was designed to compare the effects of purified antibodies against the β1-adrenoceptor autoantibodies and total immunoglobulin G obtained during immunoadsorption on L-type Ca2+ currents, action potentials and cell shortening, in rat ventricular myocytes. Patients with dilated cardiomyopathy frequently develop autoantibodies against β1-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. Immunglobulin 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 Ca2+ current to a similar extent, but prolonged the plateau duration of action potentials to a lesser extent. Immunoglobulin G and β1-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 β1-adrenoceptors and immunoglobulin G derived from patients positive for β1-adrenoceptor autoantibodies mediate the cardiostimulatory effects via β1-adrenoceptors.
Keywords:Action Potentials, Adrenergic Beta-Agonists, Autoantibodies, Beta-1 Adrenergic Receptors, Calcium, Cardiac Myocytes, Cell Size, Dilated Cardiomyopathy, Heart Ventricles, Immunoglobulin G, Immunotherapy, Isoproterenol, L-Type Calcium Channels, Patch-Clamp Techniques, Animals, Rats
Source:Basic & Clinical Pharmacology & Toxicology
Publisher:Blackwell Publishing
Page Range:445-452
Date:1 January 2005
Official Publication:https://doi.org/10.1111/j.1742-7843.2005.pto_96607.x
PubMed:View item in PubMed

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