Premium
Effects of Immunoglobulin G from Patients with Dilated Cardiomyopathy on Rat Cardiomyocytes
Author(s) -
Christ Torsten,
Adolph Esther,
Schindelhauer Stefan,
Wettwer Erich,
Dobrev Dobromir,
Wallukat Gerd,
Ravens Ursula
Publication year - 2005
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2005.pto_96607.x
Subject(s) - immunoadsorption , isoprenaline , autoantibody , medicine , antibody , contraction (grammar) , dilated cardiomyopathy , endocrinology , myocyte , immunoglobulin g , chemistry , immunology , heart failure , stimulation
This study was designed to compare the effects of purified antibodies against the β 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 β 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. 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 Ca 2+ current to a similar extent, but prolonged the plateau duration of action potentials to a lesser extent. Immunoglobulin G and β 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 β 1 ‐adrenoceptors and immunoglobulin G derived from patients positive for β 1 ‐adrenoceptor autoantibodies mediate the cardiostimulatory effects via β 1 ‐adrenoceptors.