The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the α 1 pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same α 1 gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert--Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca 2+ concentration [Ca 2+ ] i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K + -stimulated [[Ca 2+ ] i ] i increase in the α 1A cell line but not in the α 1B , α 1C , α 1D , and α 1E cell lines, establishing the α 1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the α 1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.