1.A.2.1.16
Inward rectifying K⁺ channel, Kir4.1, encoded by the KCNJ10 gene, of 379 aas and 2 TMSs.  It is inhibited by chloroethylclonidine and pentamidine which bind in the channel (Rodríguez-Menchaca et al. 2016; Aréchiga-Figueroa et al. 2017). It is also inhibited by chloropuine which inhibits by an open pore blocking mecnanism (Marmolejo-Murillo et al. 2017). Loss-of-function mutations in the pore-forming Kir4.1 subunit cause an autosomal recessive disorder characterized by epilepsy, ataxia, sensorineural deafness and tubulopathy (SeSAME/EST syndrome) Pentamidine potently inhibited Kir4.1 channels when applied to the cytoplasmic side under inside-out patch clamp configuration (IC₅₀ = 97nM). The block was voltage dependent. Molecular modeling predicted the binding of pentamidine to the transmembrane pore region of Kir4.1 at amino acids T127, T128 and E158. Mutation of each of these residues reduced the potency of pentamidine to block Kir4.1 channels (Aréchiga-Figueroa et al. 2017). Mutations in the KCNJ10 gene are associated with a distinctive ataxia, sensorineural hearing loss and a spasticity (Morin et al. 2020). It is regulated by kidins220 (TC# 8.A.28.1.8) (Jaudon et al. 2021). Pentamidine is a potent inhibitor of Kir4.1 (Zhang et al. 2022).