Potassium inwardly rectifying channel subfamily J member 10 (Kir4.1)

Potassium inwardly rectifying channel subfamily J member 10 (Kir4.1) is a tetrameric ion channel encoded by the KCNJ10 gene that allows potassium ions to enter cells more easily than exit, contributing to the maintenance of the negative resting membrane potential, extracellular potassium buffering, and general potassium homeostasis in excitable and non-excitable tissues[5][7]. Kir4.1 is primarily expressed in astrocytes in the brain (where it is crucial for potassium and glutamate clearance), in the distal convoluted tubules of the kidney (involved in potassium recycling), and in the stria vascularis of the inner ear (critical for hearing)[5]. Mutations or dysfunction in this gene/channel are implicated in epilepsy, ataxia, sensorineural deafness, tubulopathies (EAST/SeSAME syndrome), and can also play a role in cancer and other pathologies[5][6][2]. It is a validated therapeutic target for disorders involving neuronal excitability, renal ion transport, and hearing, but targeting Kir4.1 carries significant risk of neurological, auditory, and renal side effects due to its broad physiological roles[2][5][6]. Experimental inhibitors such as VU6036720 have been developed and may help further elucidate its therapeutic potential[1].

Other names

KCNJ10Kir4.1ATP-sensitive inward rectifier potassium channel 10Inward rectifier potassium channel 4.1

Inhibition reduces potassium conductance, depolarizes membrane potential, and disrupts potassium buffering, contributing to excitability and impaired homeostasis. Modulation alters neuronal and glial cell excitability and can affect kidney and ear function.