Autoantibodies against M-2 muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects

Circulating autoantibodies against the human M-2 muscarinic receptors have been previously shown in 38% of patients with idiopathic dilated cardiomyop athy. The functional properties of these autoantibodies are reported herein . They were able to decrease the cell beating frequency of myocytes in cult ured neonatal rat heart cells in a dose-dependent manner without desensitiz ation over a period of more than 5 hours whereas the non-specific muscarini c receptor agonist carbachol also inhibited the heart cell beating frequenc y but was desensitized within 1 hour. In the same cell culture, anti-M-2 mu scarinic receptor autoantibodies were not able to induce internalization of muscarinic receptor whereas carbachol did. These results demonstrate for t he first time that anti-M, muscarinic receptor autoantibodies from patients with idiopathic dilated cardiomyopathy have stimulatory muscarinic activit y in vitro, which differ from normal muscarinic agonists by non-desensitiza tion.