Potassium calcium-activated channel subfamily N member 4 (KCa3.1) (KCa3.1)

The Potassium calcium-activated channel subfamily N member 4 (KCa3.1), encoded by the KCNN4 gene on chromosome 19q13.2, is an intermediate-conductance, voltage-independent potassium channel activated by intracellular calcium via calmodulin binding, forming homotetramers with six transmembrane domains and a selective K+ pore. It drives K+ efflux, causing membrane hyperpolarization that sustains Ca2+ influx essential for processes like T-lymphocyte activation, vascular smooth muscle proliferation, erythrocyte volume control (Gardos channel), and epithelial secretion. Expressed in T cells, macrophages, smooth muscle, endothelium, erythrocytes, and secretory epithelia, KCa3.1 regulates immune responses, vascular tone, and fluid transport. Dysregulation contributes to thrombotic diseases via smooth muscle hyperplasia and inflammation, cancers through enhanced tumor migration and survival, sickle cell dehydration, renal fibrosis, and hypertension. Pharmacological blockers like TRAM-34 and clotrimazole inhibit these pathological effects by disrupting Ca2+ signaling without broad toxicity, positioning KCa3.1 as a tractable therapeutic target in oncology, vascular, and inflammatory disorders.

Other names

KCNN4IK1IKCA1SK4hIKCa1hKCa4hSK4Gardos channel

Blockade inhibits K+ efflux, reducing Ca2+ influx, cell proliferation, migration, and activation in smooth muscle, T cells, macrophages Selective pore block prevents hyperpolarization-dependent Ca2+ signaling