Potassium voltage-gated channel subfamily D member 3 (Kv4.3) (Kv4.3)

Potassium voltage-gated channel subfamily D member 3 (Kv4.3), encoded by the KCND3 gene, is a voltage-gated potassium channel that mediates the rapidly inactivating, transient outward current (Ito) in cardiac and neuronal tissues [UniProt: Q9UK17]. In the heart, Kv4.3 is a primary determinant of the early repolarization phase (Phase 1) of the action potential, and its dysregulation is associated with Brugada syndrome and atrial fibrillation [PubMed: 23439570]. In the central nervous system, it regulates neuronal excitability and is implicated in spinocerebellar ataxia type 19/22 [NCBI Gene: 3752]. Pharmacologically, Kv4.3 is targeted by several Class I and Class III anti-arrhythmic agents, such as Flecainide and Quinidine, which inhibit the channel to prolong action potential duration [PubChem]. However, the lack of high selectivity in current drugs poses challenges, as off-target effects can lead to pro-arrhythmic risks or neurological side effects [PubMed: 22508281]. Research continues into more selective Kv4.3 modulators for treating cardiac hypertrophy and heart failure [PubMed: 28838921].

Other names

KCND3Voltage-gated potassium channel subunit Kv4.3Shal-like effector 3KSHIV

Blockade or modulation of the transient outward potassium current (Ito) to prolong the cardiac action potential duration or regulate neuronal firing rates [PubMed: 23439570].