Potassium voltage-gated channel subfamily A member 4 (Kv1.4) (Kv1.4)

Potassium voltage-gated channel subfamily A member 4 (Kv1.4), encoded by the KCNA4 gene, is a member of the Shaker-related family of voltage-gated potassium channels [1.3.1]. It is primarily expressed in the brain and heart, where it mediates the transient outward potassium current (Ito,s) and plays a critical role in the repolarization phase of action potentials [1.3.1, 1.3.3]. The specific construct fKv1.4ΔN refers to a ferret-derived Kv1.4 channel with an N-terminal deletion (residues 2-146), a modification used in research to eliminate fast N-type inactivation and study slower C-type inactivation mechanisms [1.2.1, 1.4.1]. Biologically, Kv1.4 regulates neuronal firing patterns and cardiac rhythm; its dysregulation is associated with heart failure, hypertrophy, and various neurological disorders [1.3.3, 1.3.5]. Pharmacologically, Kv1.4 is sensitive to small molecule blockers like 4-aminopyridine and quinidine, which are used to modulate cellular excitability in therapeutic contexts [1.4.2, 1.5.3]. Research using the fKv1.4ΔN construct has been instrumental in understanding how drugs interact with the channel's pore and influence its gating properties [1.4.2]. Overall, Kv1.4 serves as a key regulator of excitability across multiple organ systems, making it a significant focus for drug development in cardiovascular and neurological medicine [1.3.3, 1.3.5].

Other names

KCNA4Shaker-related subfamily member 4HK1PCN2HBK4HPCN2HUKIIKCNA4LKCNA8MCIDDSfKv1.4 (ferret ortholog)fKv1.4ΔN (N-terminal deletion construct)

Drugs targeting Kv1.4 typically act as pore blockers that physically obstruct the ion conduction pathway or as gating modifiers that alter the voltage-sensitivity or inactivation kinetics of the channel [1.3.5, 1.4.1].