The discovery of pathogenic autoantibodies of VGCC has greatly facilitated diagnosis of LEMS and improved the understanding of the underlying pathophysiologic mechanisms. Subsequent researches show the most popular antibodies are that against P/Q-type VGCCs, which cause most of the clinical symptoms of LEMS ( 55 ).

This finding suggests the presence of different epitopes of P/Q type VGCC antibodies which inhibit VGCC’s function in cerebellum, or of other additional, yet undiscovered pathogenic antibodies. Clinical, laboratory and radiological features

2016年8月30日 · Autoantibodies in LEMS patients mainly target the α1 subunit of P/Q-type VGCC. The VGCC α1 subunit consists of four repeated domains (I–IV), each with six transmembrane segments (called S1-S6) joined by linker regions.

2016年8月30日 · Herein, we review reported target epitope (s) for known antibody-mediated disorders of the nervous system, address the relevance of these studies, explore the notion of epitope spreading, and discuss the issue of double autoantibody-positive patients.

Based on epitope mapping of antibody repertoire in patients with paraneoplastic neurological syndromes and small-cell lung cancer, we generated an antibody against a major epitope in the P/Q-type VGCC and evaluated its ability to affect cerebellar VGCC function and motor behavior.

2004年10月1日 · Lambert–Eaton myasthenic syndrome, often associated with small-cell lung carcinoma, is a disease of neuromuscular transmission in which antibodies directed against voltage-gated calcium channel (VGCC) (P/Q-type) in the motor nerve terminal play a crucial role in causing a deficient quantal release of acetylcholine.

2013年11月11日 · Epitope mapping in LEMS. The VGCC is a heteromultimeric protein complex on the presynaptic motor nerve terminal membrane and consists of an α1 subunit and α 2 δ, β and possibly γ accessory subunits (Fig. 2). The α1 subunit is the ion conducting pore, whereas the other subunits modulate gating and serve as a membrane anchor 129.

2017年6月12日 · Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder that is related to the loss of functional P/Q-type voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals. Up to 60% of cases occur as a paraneoplastic disorder (SCLC-LEMS), most commonly in association with small cell lung cancer.

Voltage-Gated Calcium Channels (VGCC) are channels gated by calcium ions, found in excitable cells like neurons and muscle cells. They play a crucial role in coupling electrical signals on the cell surface to intracellular events by opening when activated.

2021年3月9日 · Synaptic vesicles release acetylcholine at sites called active zones, which contain P/Q-type voltage-gated calcium channels (VGCC) and other proteins that work together to usher the synaptic vesicle to the presynaptic terminal.