EFFECT OF LAMBERT-EATON MYASTHENIC SYNDROME ANTIBODIES ON AUTONOMIC NEURONS IN THE MOUSE

Somatic muscle weakness and autonomic symptoms characterize the autoim mune Lambert-Eaton myasthenic syndrome (LEMS). The former results from IgG autoantibody-mediated down-regulation of P/Q-type voltage-gated c alcium channels at motor nerve terminals and consequent reduction in a cetylcholine release; the basis for the autonomic symptoms is unknown. Using omega-conocoxins GVIA and MVIIC and omega-agatoxin IVA that blo ck N-, Q-, and P-type channels, we investigated ex vivo the calcium ch annels subserving transmitter release from postganglionic parasympathe tic neurons in the bladder and from postganglionic sympathetic neurons in the vas deferens of mice injected with IgG from LEMS patients or f rom controls. Calcium influx through N-, P-, and Q-type channels subse rved transmitter release from parasympathetic and sympathetic neurons in control mice. In test mice, the component of transmitter release su bserved by P-type channels was abolished by four of four LEMS IgG prep arations, that subserved by Q-type channels was significantly reduced by three, and that subserved by N-type channels by one. Thus, LEMS IgG impairs transmitter release from parasympathetic and sympathetic neur ons through down-regulation of one or more subtypes of voltage-gated c alcium channels. The results suggest chat antibody-mediated interferen ce with specific ion channel function may also underlie autonomic dysf unction occurring in other autoimmune diseases.