Inwardly rectifying potassium channel subunit Kir4.1 (Kir4.1)

Kir4.1 is an inwardly rectifying potassium channel subunit encoded by the KCNJ10 gene. It forms homomeric or heteromeric channels (primarily with Kir5.1) in glial cells of the central nervous system and in renal tubular cells. In the CNS, Kir4.1 is essential for maintaining the resting membrane potential and mediates spatial potassium buffering, which supports normal neuronal activity and prevents excitotoxicity. In the kidney, Kir4.1/Kir5.1 channels regulate electrolyte and salt handling, influencing fluid balance and blood pressure. Mutations in Kir4.1 cause neurological and renal pathologies, and the channel is increasingly studied both as a biomarker and as a therapeutic target for diuretic development, neuromodulation, and antidepressant drug action. The pharmacological toolbox for Kir4.1 is limited, but the channel’s role in epilepsy, depression, and renal diseases positions it at the forefront of ion channel drug discovery.

Other names

Kir4.1KCNJ10 (gene name)Inwardly rectifying potassium channel 4.1

Channel inhibition (blockers, e.g., fluoxetine, barium inhibit Kir4.1 activity by plugging the pore or blocking potassium flow) Selective pore block (e.g., VU720) Channel activation/modulation (e.g., VU206) Modulation of neuronal and glial excitability and potassium buffering capacity