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.

Several inwardly-rectifying (Kir) potassium channels (Kin l 1, Kir41 and Kir4 2) are characterised by their sensitivity to inhibition by intracellular H+ within the physiological range The mechanism by which these channels are regulated by intracellular pH has been the subject of intense scrutiny for over a decade, yet the molecular identity of the titratable pH-sensor remains elusive In this study we have taken advantage of the acidic intracellular environment of S cerevisiae and used a K+-auxotrophic strain to screen for mutants of Kin 1 1 with impaired pH-sensitivity In addition to the previously identified K80M mutation, this unbiased screening approach identified a novel mutation (S172T) in the second transmembrane domain (TM2) that also produces a marked reduction in pH-sensitivity through destabilization of the closed-state However, despite this extensive mutagenic approach, no mutations could be identified which removed channel pH-sensitivity or which were likely to act as a separate H+-sensor unique to the pH-sensitive Kir channels In order to explain these results we propose a model in which the pH-sensing mechanism is part of an intrinsic gating mechanism common to all Kir channels not just the pH-sensitive Kin channels In this model mutations which disrupt this pH-sensor would result in an increase, not reduction, in pH-sensitivity This has major implications for any future studies of Kir channel pH-sensitivity and explains why formal identification of these pH-sensing residues still represents a major challenge

Original publication

DOI

10.4161/chan.4.5.13006

Type

Journal article

Journal

CHANNELS

Publisher

LANDES BIOSCIENCE

Publication Date

09/2010

Volume

4

Pages

390 - 397

Addresses

Tucker, SJ, Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

Keywords

pH-sensitivity, Kir channel, pH-sensor, potassium channel, Kirl 1, RECTIFIER K+ CHANNELS, POTASSIUM CHANNELS, INTRACELLULAR PH, PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE, SENSORINEURAL DEAFNESS, SURFACE EXPRESSION, BARTTER-SYNDROME, ROMK, MODULATION, MUTATIONS