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Potassium voltage-gated channel subfamily D member 3 (KCND3), commonly referred to as Kv4.3, is the primary molecular component responsible for the fast transient outward potassium current (Ito,f) in the human heart, particularly in the atria (UniProt, P51792). This current plays a critical role in the early repolarization phase (Phase 1) of the cardiac action potential, which determines the height and duration of the action potential plateau (PubMed, PMID: 15133004). In the atria, Ito is a major determinant of the effective refractory period, making it a significant target for anti-arrhythmic therapy, particularly for atrial fibrillation (PubMed, PMID: 11854044). Mutations or altered expression of KCND3 are associated with Brugada syndrome, atrial fibrillation, and heart failure (PubMed, PMID: 24585964). Drugs targeting this channel, such as vernakalant and flecainide, aim to modulate atrial excitability, though achieving atrial selectivity remains a therapeutic challenge to avoid ventricular side effects (DrugBank, DB06211).
Inhibition of the transient outward potassium current (Ito) to prolong the atrial action potential duration and effective refractory period, thereby terminating or preventing re-entrant arrhythmias (PubMed, PMID: 11854044).
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