Voltage-gated Ca2+ channels (CaV), enable the passage of Ca2+ ions in a voltage dependent manner. These heteromeric entities are formed in part by the pore-forming α1 subunit which determines the biophysical and pharmacological properties of the channel1.
CaV1 and CaV2 channels are high-voltage activated (HVA) CaV channels. The a1 subunit of these channels normally interacts and associates with α2δ subunit, a membrane anchored protein and CaVβ, a cytosolic protein1.
Four α2δ subunits have been cloned to date: α2δ1- 4. This subunit originates from a single gene. The corresponding protein is modified by post-translational cleavage yielding a α2 subunit which is disulfide bonded to the δ subunit2. All α2δ subunits are GPI- (glycosylphosphatidylinositol) anchored proteins3. The role of this subunit is important for the membrane trafficking of the α1 subunit, and also has a role in influencing the biophysical properties of the channel1.
α2δ can be expressed as various splice variants and expressed in a tissue specific manner. α2δ2 can be detected in the brain, heart, lung, spleen and liver4.
Gabapentin and pregabalin are two commonly used anti-epileptic drugs. They act on CaV channels via the α2δ1 and α2δ2 subunits by disturbing their membrane trafficking, thereby decreasing Ca2+ currents.
