Calcium-activated potassium channel subfamily N member 4 (KCa3.1 (also known as KCNN4))

Calcium-activated potassium channel subfamily N member 4 (KCa3.1, encoded by the KCNN4 gene) is an intermediate conductance potassium channel regulated by intracellular Ca²⁺ levels[2][3][7]. It couples increases in cytosolic Ca²⁺ to hyperpolarization of the cell membrane by permitting K⁺ efflux, thus regulating membrane potential, cell excitability, and Ca²⁺ signaling[2][3]. KCa3.1 plays essential roles in a variety of tissues, including endothelium (modulating vasodilation), immune cells (modulating activation and proliferation), and cancer cells (contributing to cell proliferation and migration)[2][3][5]. Specific inhibitors such as Senicapoc and TRAM-34 have shown promise in the treatment of diseases like sickle cell anemia, cancer, and inflammatory conditions[5]. KCa3.1 is considered a valid therapeutic target, but modulation of its activity can impact physiological processes in multiple organ systems, which presents safety considerations[5].

Other names

Intermediate conductance calcium-activated potassium channel 1IK channelSK4 channelKCNN4KCa3.1

Channel inhibition (blockers such as Senicapoc and TRAM-34 block K⁺ efflux and downstream effects); Channel modulation (alteration of Ca²⁺-dependent K conductance)