Lambe-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs. In normal neuromuscular function, a nerve impulse is carried down the axon (the long projection of a nerve cell) from the spinal cord. At the nerve ending in the neuromuscular junction, where the impulse is transferred to the muscle cell, the nerve impulse leads to the opening of voltage-gated calcium channels (VGCC), the influx of calcium ions into the nerve terminal, and the calcium-dependent triggering of synaptic vesicle fusion with plasma membrane. These synaptic vesicles contain acetylcholine, which is released into the synaptic cleft and stimulates the acetylcholine receptors on the muscle. The muscle then contracts. In LEMS, antibodies against VGCC, paicularly the P/Q-type VGCC, decrease the amount of calcium that can enter the nerve ending, hence less acetylcholine can be released from the neuromuscular junction. Apa from skeletal muscle, the autonomic nervous system also requires acetylcholine neurotransmission; this explains the occurrence of autonomic symptoms in LEMSP/Q voltage-gated calcium channels are also found in the cerebellum, explaining why some experience problems with coordination. The antibodies bind paicularly to the pa of the receptor known as the "domain III S5-S6 linker peptide".Antibodies may also bind other VGCCs.Some have antibodies that bind synaptotagmin, the protein sensor for calcium-regulated vesicle fusion.Many people with LEMS, both with and without VGCC antibodies, have detectable antibodies against the M1 subtype of the acetylcholine receptor; their presence may paicipate in a lack of compensation for the weak calcium influx anti p/Q antibodies are produced against voltage gated channels mainly P/Q voltage gates Ref Harrison 20th edition pg 567