Potassium voltage-gated channel subfamily A member 2 (Kv1.2) (Kv1.2)

The Potassium voltage-gated channel subfamily A member 2 (Kv1.2), encoded by the KCNA2 gene, is a critical component of the nervous system's electrical signaling apparatus [UniProt, NIH]. As a member of the Shaker-related 'delayed rectifier' family, it forms tetrameric channels that open in response to membrane depolarization, allowing potassium ions to flow out of the cell and reset the membrane potential [Wikipedia, NIH]. This process is essential for regulating neuronal excitability, action potential frequency, and the release of neurotransmitters at synaptic terminals [UniProt, MDPI]. Mutations in the KCNA2 gene are linked to a variety of severe neurological conditions, most notably developmental and epileptic encephalopathy type 32 (DEE32), which is characterized by early-onset seizures, ataxia, and intellectual disability [NIH, ResearchGate]. These pathogenic variants are categorized into gain-of-function, loss-of-function, or mixed-type effects, which dictate the specific clinical presentation and therapeutic response [KCNA2 Epilepsy Foundation, PubMed]. Pharmacologically, the channel is a target for the potassium channel blocker 4-aminopyridine (dalfampridine), which has shown efficacy in reducing seizure frequency and improving motor function specifically in patients with gain-of-function mutations [Wikipedia, AES]. Additionally, the channel is sensitive to various peptide toxins from snake and scorpion venoms, such as dendrotoxins, which are frequently used as molecular probes in research to study channel kinetics and pore structure [eLife, NIH].

Other names

KCNA2RBK2NGK1HBK5HuKIVVoltage-gated potassium channel protein Kv1.2Shaker-related subfamily member 2

Potassium channel blockade to antagonize gain-of-function variants; modulation of voltage-dependent gating and ion conductance.