Paraneoplastic myasthenic syndrome IgG inhibits ⁴⁵Ca²⁺ flux in a human small cell carcinoma line

Abstract

Certain cancers exert unexplained remote effects on the nervous system¹. Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis² and which is of possible neural crest origin³, is present in ∼70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS)⁴, a disorder characterized by fatigable muscle weakness. Patients with this syndrome have a defect in the (Ca²⁺-dependent) quantal release of acetylcholine from motor nerve terminals evoked by a nerve impulse or by high K⁺ (ref. 5), and a decreased number of presynaptic active zone particles⁶. The physiological and morphological features of the syndrome can be transferred to mice by the patients' IgG, consistent with an autoantibody interfering with the function of voltage-dependent Ca²⁺ channels^7–10. Here we demonstrate that K⁺-induced ⁴⁵Ca²⁺ flux in a cultured human SCC line is significantly reduced by LEMS IgG, suggesting that in SCC-LEMS an autoantibody to tumour Ca²⁺-channel determinants is triggered; its cross-reaction with similar determinants at the motor nerve terminal could lead to the remote neurological syndrome.