CACNA1B

CACNA1B is the gene that encodes the alpha-1B subunit of voltage-gated calcium channels, also known as Cav2.2. This pore-forming subunit belongs to the Cav2 family and is essential for calcium influx in neurons on membrane depolarization. In the nervous system, Cav2.2 channels are enriched at presynaptic terminals and play a key role in translating electrical activity into neurotransmitter release, thereby contributing to synaptic transmission and pain signaling.

The alpha-1B subunit is a large transmembrane protein composed of four homologous domains (I–IV). Each domain contains six transmembrane segments, including the voltage-sensing S4 segment and the pore-forming loop between S5 and S6. Channel function is modulated by auxiliary subunits such as beta and alpha2delta, which influence trafficking, kinetics, and expression at the cell surface.

Pharmacology and clinical relevance: N-type channels encoded by CACNA1B are inhibited by certain peptide toxins (omega-conotoxins) and by clinically used analgesics such as ziconotide, a drug that blocks Cav2.2 to reduce neurotransmitter release and alleviate severe chronic pain.

Genetic and expression context: Variants in CACNA1B have been investigated in relation to various neurological conditions, including epilepsy, migraine, and other neuropsychiatric disorders, as well as pain syndromes. Evidence for causal roles remains inconclusive and is the subject of ongoing research. The gene is broadly expressed in the nervous system, with detectable expression in regions involved in nociception and synaptic transmission.