IgGs and Mabs against the β2-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 beta(2)-adrenoceptor induced conduction blocks which could be washed away by the beta(2)-adrenoceptor inverse agonist IC1118,551, confirming the specificity and non-toxicity of these events. These results were confirmed by the use of a monoclonal antibody, monospecific for the beta(2)-adrenoceptor and the beta(2)-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 beta(1)-adrenoceptor, highly increased the beating frequency without interfering with the conduction. Our results suggest that stimulation of the beta(2)-adrenoceptor by antireceptor antibodies in the conduction tissues leads to conduction disturbances, probably mediated by coupling to a different pathway than the classical G(s) pathway. They confirm that anti-beta(2) adrenoceptor antibodies could be responsible for ventricular arrhythmias. (c) 2006 Elsevier Inc. All rights reserved.