ArticleChannels (Austin, Tex.)
Random mutagenesis screening indicates the absence of a separate H(+)-sensor in the pH-sensitive Kir channels.
Article in Channels (Austin, Tex.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance.Molecular biology of the cell · 2024Article
- Genome mining yields putative disease-associated ROMK variants with distinct defects.PLoS genetics · 2023Article
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- Complementary computational and experimental evaluation of missense variants in the ROMK potassium channel.PLoS computational biology · 2020Article
- Review
- The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK).The Journal of biological chemistry · 2018Article
- Inwardly Rectifying KNeurochemical research · 2017Article
- Endoplasmic reticulum-associated degradation of the renal potassium channel, ROMK, leads to type II Bartter syndrome.The Journal of biological chemistry · 2017Article
- Article
- Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels.Physiological reviews · 2015Review
- Tethered protein display identifies a novel Kir3.2 (GIRK2) regulator from protein scaffold libraries.ACS chemical neuroscience · 2014Article
- State-dependent network connectivity determines gating in a K+ channel.Structure (London, England : 1993) · 2014Article
- Control of KirBac3.1 potassium channel gating at the interface between cytoplasmic domains.The Journal of biological chemistry · 2014Article
- Insights into the structural nature of the transition state in the Kir channel gating pathway.Channels (Austin, Tex.) · 2014Article
- Using yeast to study potassium channel function and interactions with small molecules.Methods in molecular biology (Clifton, N.J.) · 2013Article
- The salt-wasting phenotype of EAST syndrome, a disease with multifaceted symptoms linked to the KCNJ10 K+ channel.Pflugers Archiv : European journal of physiology · 2011Review
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5 authors.
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Abstract
Several inwardly-rectifying (Kir) potassium channels (Kir1.1, Kir4.1 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 Kir1.1 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 Kir 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.
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