Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2004 Oct 01;560Pt 1:51-62. doi: 10.1113/jphysiol.2004.070292.
Show Gene links
Show Anatomy links
Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc.
Clarke CE
,
Veale EL
,
Green PJ
,
Meadows HJ
,
Mathie A
.
???displayArticle.abstract???
Background potassium channels control the resting membrane potential of neurones and regulate their excitability. Two-pore-domain potassium (2-PK) channels have been shown to underlie a number of such neuronal background currents. Currents through human TASK-1, TASK-2 and TASK-3 channels expressed in Xenopus oocytes were inhibited by extracellular acidification. For TASK-3, mutation of histidine 98 to aspartate or alanine considerably reduced this effect of pH. Zinc was found to be a selective blocker of TASK-3 with virtually no effect on TASK-1 or TASK-2. Zinc had an IC(50) of 19.8 microM for TASK-3, at +80 mV, with little voltage dependence associated with this inhibition. TASK-3 H98A had a much reduced sensitivity to zinc suggesting this site is important for zinc block. Surprisingly, TASK-1 also has histidine in position 98 but is insensitive to zinc block. TASK-3 and TASK-1 differ at position 70 with glutamate for TASK-3 and lysine for TASK-1. TASK-3 E70K also had a much reduced sensitivity to zinc while the corresponding reverse mutation in TASK-1, K70E, induced zinc sensitivity. A TASK-3-TASK-1 concatamer channel was comparatively zinc insensitive. For TASK-3, it is concluded that positions E70 and H98 are both critical for zinc block. The native cerebellar granule neurone (CGN) leak current, IK(SO), is sensitive to block by zinc, with current reduced to 0.58 of control values in the presence of 100 microM zinc. This suggests that TASK-3 channels underlie a major component of IK(SO). It has recently been suggested that zinc is released from inhibitory synapses onto CGNs. Therefore it is possible that inhibition of IK(SO) in cerebellar granule cells by synaptically released zinc may have important physiological consequences.
Auld,
Zinc coordination sphere in biochemical zinc sites.
2001, Pubmed
Auld,
Zinc coordination sphere in biochemical zinc sites.
2001,
Pubmed
Barbuti,
Block of the background K(+) channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor.
2002,
Pubmed
Brickley,
Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance.
2001,
Pubmed
Buckler,
An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells.
2000,
Pubmed
Chapman,
Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel.
2000,
Pubmed
,
Xenbase
Clyne,
The role of histidine residues in modulation of the rat P2X(2) purinoceptor by zinc and pH.
2002,
Pubmed
,
Xenbase
Czirják,
TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II.
2000,
Pubmed
,
Xenbase
Czirják,
Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits.
2002,
Pubmed
,
Xenbase
Czirják,
Ruthenium red inhibits TASK-3 potassium channel by interconnecting glutamate 70 of the two subunits.
2003,
Pubmed
Frederickson,
Zinc-containing neurons.
1994,
Pubmed
Frederickson,
Imaging zinc: old and new tools.
2003,
Pubmed
Gallo,
The role of depolarization in the survival and differentiation of cerebellar granule cells in culture.
1987,
Pubmed
Gibbs,
Regionally selective blockade of GABAergic inhibition by zinc in the thalamocortical system: functional significance.
2000,
Pubmed
Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed
Han,
Characterization of four types of background potassium channels in rat cerebellar granule neurons.
2002,
Pubmed
Harrison,
Zn2+: an endogenous modulator of ligand- and voltage-gated ion channels.
1994,
Pubmed
Hartness,
Combined antisense and pharmacological approaches implicate hTASK as an airway O(2) sensing K(+) channel.
2001,
Pubmed
Herrup,
The compartmentalization of the cerebellum.
1997,
Pubmed
Hosie,
Zinc-mediated inhibition of GABA(A) receptors: discrete binding sites underlie subtype specificity.
2003,
Pubmed
Huang,
Metal ions and synaptic transmission: think zinc.
1997,
Pubmed
Huston,
Pertussis toxin treatment increases glutamate release and dihydropyridine binding sites in cultured rat cerebellar granule neurons.
1993,
Pubmed
Kang,
Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells.
2004,
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
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,
Molecular and functional properties of two-pore-domain potassium channels.
2000,
Pubmed
Lesage,
Pharmacology of neuronal background potassium channels.
2003,
Pubmed
Li,
Induction of mossy fiber --> Ca3 long-term potentiation requires translocation of synaptically released Zn2+.
2001,
Pubmed
Li,
Do we need zinc to think?
2003,
Pubmed
Lopes,
Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers.
2001,
Pubmed
,
Xenbase
Maingret,
The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1.
2001,
Pubmed
Mathie,
What are the roles of the many different types of potassium channel expressed in cerebellar granule cells?
2003,
Pubmed
Meadows,
Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.
2001,
Pubmed
,
Xenbase
Meuth,
Contribution of TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 channels to the control of activity modes in thalamocortical neurons.
2003,
Pubmed
Millar,
A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.
2000,
Pubmed
,
Xenbase
Minami,
Relationship between zinc and neurotransmitters released into the amygdalar extracellular space.
2002,
Pubmed
Morton,
Determinants of pH sensing in the two-pore domain K(+) channels TASK-1 and -2.
2003,
Pubmed
,
Xenbase
Mu,
Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene.
2003,
Pubmed
O'Connell,
Two-pore domain K+ channels-molecular sensors.
2002,
Pubmed
Pei,
Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function.
2003,
Pubmed
,
Xenbase
Rajan,
TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor.
2000,
Pubmed
,
Xenbase
Ruiz,
Endogenous zinc inhibits GABA(A) receptors in a hippocampal pathway.
2004,
Pubmed
Sano,
A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord.
2003,
Pubmed
Smart,
Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.
1994,
Pubmed
Suh,
Release of synaptic zinc is substantially depressed by conventional brain slice preparations.
2000,
Pubmed
Takayasu,
Muscarine-induced increase in frequency of spontaneous EPSCs in Purkinje cells in the vestibulo-cerebellum of the rat.
2003,
Pubmed
Takeda,
Movement of zinc and its functional significance in the brain.
2000,
Pubmed
Talley,
Cns distribution of members of the two-pore-domain (KCNK) potassium channel family.
2001,
Pubmed
Talley,
TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons.
2000,
Pubmed
Wang,
Inhibitory zinc-enriched terminals in the mouse cerebellum: double-immunohistochemistry for zinc transporter 3 and glutamate decarboxylase.
2002,
Pubmed
Watkins,
A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons.
1996,
Pubmed
Weiss,
Zn(2+): a novel ionic mediator of neural injury in brain disease.
2000,
Pubmed
