F
IPR003092

Two pore domain potassium channel, TASK family

InterPro entry
Short name2pore_dom_K_chnl_TASK
family relationships

Description

2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+ in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.

The first member of this family (TOK1), cloned from Saccharomyces cerevisiae
[4]
, is predicted to have eight potential transmembrane (TM) helices. However, subsequently-cloned two P-domain family members from Drosophila and mammalian species are predicted to have only four TM segments. They are usually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel)
[1, 3, 2, 5]
. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology of four TM segments, including two P-domains. That TWIK-related K+ channels all produce instantaneous and non-inactivating K+ currents, which do not display a voltage-dependent activation threshold, suggests that they are background (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.

TASK is a member of the TWIK-related (two P-domain) K+channel family identified in human tissues
[5]
. It is widely distributed, being particularly abundant in the pancreas and placenta, but it is also found in the brain, heart, lung and kidney. Its amino acid identity to TWIK-1 and TREK-1 is rather low, being about 25-28%. However, it is thought to share the same topology of four TM segments, with two P-domains. TASK is very sensitive to variations in extracellular pH in the physiological range, changing from fully-open to closed in approximately 0.5 pH units around pH 7.4. Thus, it may well be a biological sensor of external pH variations.

References

1.ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae. Goldstein SA, Price LA, Rosenthal DN, Pausch MH. Proc. Natl. Acad. Sci. U.S.A. 93, 13256-61, (1996). View articlePMID: 8917578

2.TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J. EMBO J. 15, 1004-11, (1996). View articlePMID: 8605869

3.Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M. EMBO J. 15, 6854-62, (1996). View articlePMID: 9003761

4.A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Ketchum KA, Joiner WJ, Sellers AJ, Kaczmarek LK, Goldstein SA. Nature 376, 690-5, (1995). View articlePMID: 7651518

5.TASK, a human background K+ channel to sense external pH variations near physiological pH. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. EMBO J. 16, 5464-71, (1997). View articlePMID: 9312005

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