Guinea pig Anti-K_V2.1 Antibody

Voltage gated K+ channels are involved in diverse physiological processes ranging from repolarization of neuronal and cardiac action potential, regulation of Ca²⁺ signaling and cell volume to driving cellular proliferation and migration.

K_V2.1 consists of four α-subunits, each containing six transmembrane α-helical segments, S1-S6, and a membrane-re-entering P-loop, which are arranged circumferentially around a central pore. This ion conduction pore is lined by four S5-P-S6 sequences. The four first segments(1-4), each containing four positively charged arginine residues in the Segment number 4 helix, act as voltage sensor domains and “gate” the pore by “pulling” on the segments 4 and 5 linker.

K_V2.1, encoded by the KCNB1 gene, is a classical delayed rectifier channel that is involved in neuronal repolarization. Its function can be diversified through heteromultimerization with “silent” KV units, which modify inactivation, trafficking, drug sensitivity and expression.

Inhibition of K_V2.1 in pancreatic β-cells enhances insulin secretion, suggesting a potential therapeutic strategy for type 2 diabetes. This effect is presumed to occur through non-conducting functions - namely, a physical interaction with syntaxin (a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex) that facilitates vesicle fusion¹.

Recently, a “de novo” pathogenic K_V2.1 variant was discovered in a family suffering from idiopathic epileptic encephalopathy. This variant is a missense mutation in the coding region of the KCNB1 gene. Expression of the V378A variant results in voltage-activated currents that are sensitive to the selective K_V2 channel blocker guangxitoxin-1E. Currents through the mutant channel are non-selective among monovalent cations².