Potassium voltage-gated channel subfamily A member 5 (KCNA5) (hKv1.5)

Potassium voltage-gated channel subfamily A member 5 (hKv1.5), encoded by the KCNA5 gene, is a voltage-gated potassium channel that mediates the ultra-rapid delayed rectifier potassium current (IKur) in the human heart [1, 4]. It is primarily expressed in the atria and is notably absent from the ventricles, making it a highly attractive therapeutic target for atrial fibrillation (AF) to avoid ventricular pro-arrhythmia [4, 11]. Beyond the heart, hKv1.5 is found in pulmonary artery smooth muscle cells (PASMCs), where it regulates vascular tone and cell proliferation; its dysfunction or inhibition is linked to idiopathic pulmonary arterial hypertension (IPAH) [3]. In oncology, overexpression of hKv1.5 has been observed in various cancer types, suggesting a role in cell cycle progression and tumor growth [1, 10]. Pharmacological inhibition of hKv1.5 by drugs like vernakalant aims to prolong atrial refractoriness to treat AF [5, 6]. However, achieving high selectivity over other Kv1 family members (such as Kv1.1-1.3) remains a significant challenge in drug development to avoid off-target effects [4, 13].

Other names

KCNA5Kv1.5HK2HPCN1Voltage-gated potassium channel subunit Kv1.5hKv1.5

Blockade of the ultra-rapid delayed rectifier potassium current (IKur)