IgGs and Mabs against the beta2-adrenoreceptor block A-V conduction in mouse hearts: A possible role in the pathogenesis of ventricular arrhythmias.
Autoantibodies against beta-adrenoceptors might be involved in different cardiomyopathic diseases such as idopathic dilated cardiomyopathy, Chagas' disease and ventricular arrhythmias. To study the effects of such antibodies on the whole heart, we made use of a new technique allowing the measurement of Ca++ transients as well as action potentials in Langendorff preparations of mouse hearts. Mouse antibodies directed against the second extracellular loop of the beta2-adrenoceptor induced conduction blocks which could be washed away by the beta2-adrenoceptor inverse agonist ICI118,551, confirming the specificity and non-toxicity of these events. These results were confirmed by the use of a monoclonal antibody, monospecific for the beta2-adrenoceptor and the beta2-specific full agonist, clenbuterol. Both increased slightly, but significantly, the beating frequency but their main effect was the production of conduction blocks. In contrast, a monoclonal antibody, monospecific for the beta1-adrenoceptor, highly increased the beating frequency without interfering with the conduction. Our results suggest that stimulation of the beta2-adrenoceptor by anti-receptor antibodies in the conduction tissues leads to conduction disturbances, probably mediated by coupling to a different pathway than the classical Gs pathway. They confirm that anti-beta2 adrenoceptor antibodies could be responsible for ventricular arrhythmias.
Escobar
Ariel L
AL
Department of Physiology, Texas Tech University Health Sciences Center, 3601 4th St. Lubbock, TX 79430, USA.
Fernández-Gómez
Rodolfo
R
Peter
Jean-Christophe
JC
Mobini
Reza
R
Hoebeke
Johan
J
Mijares
Alfredo
A
D000200:Action Potentials; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000473:pathology / Q000503:physiopathology*; D020013:Calcium Signaling / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology / Q000378:metabolism
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2