Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The pH-sensitive renal potassium channel Kir1.1 is important for K+ homeostasis. Disruption of the pH-sensing mechanism causes type II Bartter syndrome. The pH sensor is thought to be an anomalously titrated lysine residue (K80) that interacts with two arginine residues as part of an 'RKR triad'. We show that a Kir1.1 orthologue from Fugu rubripes lacks this lysine and yet is still highly pH sensitive, indicating that K80 is not the H+ sensor. Instead, K80 functionally interacts with A177 on transmembrane domain 2 at the 'helix-bundle crossing' and controls the ability of pH-dependent conformational changes to induce pore closure. Although not required for pH inhibition, K80 is indispensable for the coupling of pH gating to the extracellular K+ concentration, explaining its conservation in most Kir1.1 orthologues. Furthermore, we demonstrate that instead of interacting with K80, the RKR arginine residues form highly conserved inter- and intra-subunit interactions that are important for Kir channel gating and influence pH sensitivity indirectly.

Original publication




Journal article



Publication Date





611 - 616


Amino Acid Sequence, Amino Acid Substitution, Animals, Arginine, Computer Simulation, Conserved Sequence, Dose-Response Relationship, Drug, Electrophysiology, Female, Hydrogen-Ion Concentration, Microinjections, Models, Molecular, Molecular Sequence Data, Oocytes, Patch-Clamp Techniques, Phosphatidylinositol 4,5-Diphosphate, Potassium, Potassium Channels, Inwardly Rectifying, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Subunits, RNA, Messenger, Sequence Homology, Amino Acid, Structure-Activity Relationship, Time Factors, Xenopus