Calcium channel subunit alpha2delta-2 (CACNA2D2)

Calcium channel subunit alpha2delta-2 is an auxiliary subunit of high-voltage-activated (HVA) voltage-gated calcium channels, encoded by the CACNA2D2 gene. It forms part of a heteromeric channel complex alongside the principal pore-forming alpha1 subunit and other auxiliary subunits. Alpha2delta-2 is critical for trafficking and functional expression of CaV1 and CaV2 family channels, modulating their density, voltage-dependence, and kinetic properties at the cell surface. It plays an important role in regulating presynaptic calcium entry and neurotransmitter release, especially in the central nervous system. The subunit is a functional target for gabapentinoid drugs, which bind to it and inhibit its normal trafficking function, thus reducing neuronal excitability in conditions such as neuropathic pain and epilepsy. Dysfunction of alpha2delta-2 is associated with cerebellar ataxia and epilepsy in both human disease and animal models.

Other names

CACNA2D2Alpha-2/delta-2 subunitVoltage-dependent calcium channel subunit alpha-2/delta-2

Gabapentinoid class drugs (e.g., gabapentin, pregabalin) bind to the alpha2delta-2 subunit, inhibiting its function. This impairs the trafficking of calcium channels to the plasma membrane, reduces calcium influx into neurons, and thereby decreases neurotransmitter release, producing analgesic and anticonvulsant effects.