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We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels non-selective. We interpret the effects of these--and of other mutations--in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter.
Ashmole,
TASK-5, a novel member of the tandem pore K+ channel family.
2001, Pubmed,
Xenbase
Ashmole,
TASK-5, a novel member of the tandem pore K+ channel family.
2001,
Pubmed
,
Xenbase
Bayliss,
TASK-1 is a highly modulated pH-sensitive 'leak' K(+) channel expressed in brainstem respiratory neurons.
2001,
Pubmed
Bezanilla,
Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons.
1972,
Pubmed
Bichet,
Merging functional studies with structures of inward-rectifier K(+) channels.
2003,
Pubmed
Bockenhauer,
KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel.
2001,
Pubmed
,
Xenbase
Buckler,
An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells.
2000,
Pubmed
Chapman,
GYGD pore motifs in neighbouring potassium channel subunits interact to determine ion selectivity.
2001,
Pubmed
Claydon,
Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K(+) channel.
2002,
Pubmed
,
Xenbase
Cordero-Morales,
Molecular determinants of gating at the potassium-channel selectivity filter.
2006,
Pubmed
Cordero-Morales,
Voltage-dependent gating at the KcsA selectivity filter.
2006,
Pubmed
Czirják,
Inhibition of TASK-1 potassium channel by phospholipase C.
2001,
Pubmed
,
Xenbase
Czirják,
The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin.
2004,
Pubmed
,
Xenbase
Decher,
Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family.
2001,
Pubmed
,
Xenbase
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Duprat,
TASK, a human background K+ channel to sense external pH variations near physiological pH.
1997,
Pubmed
,
Xenbase
Girard,
Genomic and functional characteristics of novel human pancreatic 2P domain K(+) channels.
2001,
Pubmed
,
Xenbase
Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed
Hajdú,
Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel.
2003,
Pubmed
,
Xenbase
Heginbotham,
Mutations in the K+ channel signature sequence.
1994,
Pubmed
,
Xenbase
Jentsch,
Physiological functions of CLC Cl- channels gleaned from human genetic disease and mouse models.
2005,
Pubmed
Karschin,
Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K(+) channel subunit, TASK-5, associated with the central auditory nervous system.
2001,
Pubmed
,
Xenbase
Kehl,
Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn(2+).
2002,
Pubmed
Kim,
Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1).
1998,
Pubmed
,
Xenbase
Kim,
TASK-5, a new member of the tandem-pore K(+) channel family.
2001,
Pubmed
Kim,
TASK-3, a new member of the tandem pore K(+) channel family.
2000,
Pubmed
Lauritzen,
K+-dependent cerebellar granule neuron apoptosis. Role of task leak K+ channels.
2003,
Pubmed
Leonoudakis,
An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum.
1998,
Pubmed
,
Xenbase
Lesage,
Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.
1996,
Pubmed
,
Xenbase
Lesage,
Molecular and functional properties of two-pore-domain potassium channels.
2000,
Pubmed
Li,
Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.
2003,
Pubmed
,
Xenbase
Lopes,
Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers.
2001,
Pubmed
,
Xenbase
Lopes,
Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3.
2000,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
MacKinnon,
Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels.
1990,
Pubmed
Maingret,
Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K(+) channel.
2002,
Pubmed
McGuffin,
The PSIPRED protein structure prediction server.
2000,
Pubmed
Morton,
Determinants of pH sensing in the two-pore domain K(+) channels TASK-1 and -2.
2003,
Pubmed
,
Xenbase
O'Connell,
Selectivity and interactions of Ba2+ and Cs+ with wild-type and mutant TASK1 K+ channels expressed in Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Patel,
Properties and modulation of mammalian 2P domain K+ channels.
2001,
Pubmed
Pei,
Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function.
2003,
Pubmed
,
Xenbase
Prole,
Mechanisms underlying modulation of neuronal KCNQ2/KCNQ3 potassium channels by extracellular protons.
2003,
Pubmed
Rajan,
TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor.
2000,
Pubmed
,
Xenbase
Reyes,
Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney.
1998,
Pubmed
Sali,
Comparative protein modelling by satisfaction of spatial restraints.
1993,
Pubmed
So,
The K+ channel signature sequence of murine Kir2.1: mutations that affect microscopic gating but not ionic selectivity.
2001,
Pubmed
Somodi,
pH-dependent modulation of Kv1.3 inactivation: role of His399.
2004,
Pubmed
Stanfield,
Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
2002,
Pubmed
Starkus,
Mechanisms of the inhibition of Shaker potassium channels by protons.
2003,
Pubmed
,
Xenbase
Taglialatela,
Regulation of K+/Rb+ selectivity and internal TEA blockade by mutations at a single site in K+ pores.
1993,
Pubmed
Tosatto,
A divide and conquer approach to fast loop modeling.
2002,
Pubmed
Wood,
Structure of intact AhpF reveals a mirrored thioredoxin-like active site and implies large domain rotations during catalysis.
2001,
Pubmed
Yellen,
The moving parts of voltage-gated ion channels.
1998,
Pubmed
Yuill,
The selectivity filter of the tandem pore potassium channel TASK-1 and its pH-sensitivity and ionic selectivity.
2004,
Pubmed
,
Xenbase
Zhou,
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.
2001,
Pubmed
Zilberberg,
KCNKØ: opening and closing the 2-P-domain potassium leak channel entails "C-type" gating of the outer pore.
2001,
Pubmed
,
Xenbase
