Autoantibody-Mediated Channelopathies at the Neuromuscular Junction

Abstract

The neuromuscular junction is vulnerable to antibody-mediated autoimmune attack, probably because it lacks the protection of the blood-brain barrier. This review focuses on three disorders: myasthenia gravis (MG) and the Lambert-Eaton myasthenic syndrome (LEMS), in both of which there is fatiguable muscle weakness, and acquired neuromyotonia (ANMT), in which hyperexcitable peripheral nerves lead to continuous muscle fiber activity and sometimes parasthesias. Each can occur as a paraneoplastic disorder (thymoma in MG and ANMT, and small cell lung cancer in LEMS). The clinical abnormalities are improved following plasmapheresis (which removes circulating antibodies), and injection of experimental animals with immunoglobulins of patients transfers the pathophysiological changes. The ion channel targets in these three disorders are the muscle acetylcholine receptor (a ligand-gated cation channel) in MG, nerve terminal and autonomic voltage-gated calcium channels in LEMS, and peripheral nerve voltage-gated potassium channels in ANMT. The autoantibody attack results in a reduced number of functional channels. Each of the autoantibodies can be detected in serum by immunoassay. These discoveries have allowed new approaches to treatment and suggest that there may be other undiscovered antibody-mediated ion channelopathies. NEUROSCIENTIST 3:337–346, 1997