In vivo mobility of beta-adrenergic receptors and the effect of cardiac autoantibodies against beta-adren-ergic receptors

摘要

Autoantibodies directed against cardiac beta-adrenergic receptors (beta_1- and beta_2-AR) are observed in idiopathic dilated cardiomyopathy (DCM) and are suggested to play a key role in the etiology of DCM by altering the receptor mobility, internalization and/or degradation. Here we report that the agonist isoproterenol, but not cardiac autoantibodies bound to (beta)ARs stimulates receptor internalization, and that beta_1- and beta_2AR differently undergo internalization during isoproterenol treatment. Moreover, uninduced receptors exhibit a high lateral mobility on the cell membrane. The data presented here suggest that (beta)ARs are mobile membrane proteins, and addition of an agonist alters receptor dynamics, whereas cardiac autoantibodies may only sensitize (beta)ARs.