Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1996 Mar 1;15(5):1004–1011.

TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure.

F Lesage 1, E Guillemare 1, M Fink 1, F Duprat 1, M Lazdunski 1, G Romey 1, J Barhanin 1
PMCID: PMC449995  PMID: 8605869

Abstract

A new human weakly inward rectifying K+ channel, TWIK-1, has been isolated. This channel is 336 amino acids long and has four transmembrane domains. Unlike other mammalian K+ channels, it contains two pore-forming regions called P domains. Genes encoding structural homologues are present in the genome of Caenorhabditis elegans. TWIK-1 currents expressed in Xenopus oocytes are time-independent and present a nearly linear I-V relationship that saturated for depolarizations positive to O mV in the presence of internal Mg2+. This inward rectification is abolished in the absence of internal Mg2+. TWIK-1 has a unitary conductance of 34 pS and a kinetic behaviour that is dependent on the membrane potential. In the presence of internal Mg2+, the mean open times are 0.3 and 1.9 ms at -80 and +80 mV, respectively. The channel activity is up-regulated by activation of protein kinase C and down-regulated by internal acidification. Both types of regulation are indirect. TWIK-1 channel activity is blocked by Ba2+(IC50=100 microM), quinine (IC50=50 microM) and quinidine (IC50=95 microM). This channel is of particular interest because its mRNA is widely distributed in human tissues, and is particularly abundant in brain and heart. TWIK-1 channels are probably involved in the control of background K+ membrane conductances.

Full text

PDF
1004

Images in this article

1005Image
on p.1005
1006Image
on p.1006

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aldrich R. W. Potassium channels. New channel subunits are a turn-off. Curr Biol. 1994 Sep 1;4(9):839–840. doi: 10.1016/s0960-9822(00)00187-1. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Attali B., Latter H., Rachamim N., Garty H. A corticosteroid-induced gene expressing an "IsK-like" K+ channel activity in Xenopus oocytes. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6092–6096. doi: 10.1073/pnas.92.13.6092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Auffray C., Behar G., Bois F., Bouchier C., Da Silva C., Devignes M. D., Duprat S., Houlgatte R., Jumeau M. N., Lamy B. IMAGE: intégration au niveau moléculaire de l'analyse du génome humain et de son expression. C R Acad Sci III. 1995 Feb;318(2):263–272. [PubMed] [Google Scholar]
  5. Barres B. A., Chun L. L., Corey D. P. Ion channels in vertebrate glia. Annu Rev Neurosci. 1990;13:441–474. doi: 10.1146/annurev.ne.13.030190.002301. [DOI] [PubMed] [Google Scholar]
  6. Bear C. E., Davison J. S., Shaffer E. A. Intracellular pH influences the resting membrane potential of isolated rat hepatocytes. Biochim Biophys Acta. 1988 Oct 6;944(2):113–120. doi: 10.1016/0005-2736(88)90424-5. [DOI] [PubMed] [Google Scholar]
  7. Betz H. Homology and analogy in transmembrane channel design: lessons from synaptic membrane proteins. Biochemistry. 1990 Apr 17;29(15):3591–3599. doi: 10.1021/bi00467a001. [DOI] [PubMed] [Google Scholar]
  8. Bezanilla F., Stefani E. Voltage-dependent gating of ionic channels. Annu Rev Biophys Biomol Struct. 1994;23:819–846. doi: 10.1146/annurev.bb.23.060194.004131. [DOI] [PubMed] [Google Scholar]
  9. Bradley J., Li J., Davidson N., Lester H. A., Zinn K. Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8890–8894. doi: 10.1073/pnas.91.19.8890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Browne D. L., Gancher S. T., Nutt J. G., Brunt E. R., Smith E. A., Kramer P., Litt M. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet. 1994 Oct;8(2):136–140. doi: 10.1038/ng1094-136. [DOI] [PubMed] [Google Scholar]
  11. Canessa C. M., Schild L., Buell G., Thorens B., Gautschi I., Horisberger J. D., Rossier B. C. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994 Feb 3;367(6462):463–467. doi: 10.1038/367463a0. [DOI] [PubMed] [Google Scholar]
  12. Curran M. E., Splawski I., Timothy K. W., Vincent G. M., Green E. D., Keating M. T. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995 Mar 10;80(5):795–803. doi: 10.1016/0092-8674(95)90358-5. [DOI] [PubMed] [Google Scholar]
  13. Doupnik C. A., Davidson N., Lester H. A. The inward rectifier potassium channel family. Curr Opin Neurobiol. 1995 Jun;5(3):268–277. doi: 10.1016/0959-4388(95)80038-7. [DOI] [PubMed] [Google Scholar]
  14. Duprat F., Lesage F., Guillemare E., Fink M., Hugnot J. P., Bigay J., Lazdunski M., Romey G., Barhanin J. Heterologous multimeric assembly is essential for K+ channel activity of neuronal and cardiac G-protein-activated inward rectifiers. Biochem Biophys Res Commun. 1995 Jul 17;212(2):657–663. doi: 10.1006/bbrc.1995.2019. [DOI] [PubMed] [Google Scholar]
  15. Guillemare E., Honoré E., Pradier L., Lesage F., Schweitz H., Attali B., Barhanin J., Lazdunski M. Effects of the level of mRNA expression on biophysical properties, sensitivity to neurotoxins, and regulation of the brain delayed-rectifier K+ channels Kv1.2. Biochemistry. 1992 Dec 15;31(49):12463–12468. doi: 10.1021/bi00164a024. [DOI] [PubMed] [Google Scholar]
  16. Guillemare E., Lazdunski M., Honoré E. Glibenclamide opens ATP-sensitive potassium channels in Xenopus oocyte follicular cells during metabolic stress. Mol Pharmacol. 1995 Mar;47(3):588–594. [PubMed] [Google Scholar]
  17. Heginbotham L., Lu Z., Abramson T., MacKinnon R. Mutations in the K+ channel signature sequence. Biophys J. 1994 Apr;66(4):1061–1067. doi: 10.1016/S0006-3495(94)80887-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Isom L. L., De Jongh K. S., Catterall W. A. Auxiliary subunits of voltage-gated ion channels. Neuron. 1994 Jun;12(6):1183–1194. doi: 10.1016/0896-6273(94)90436-7. [DOI] [PubMed] [Google Scholar]
  19. Jan L. Y., Jan Y. N. Potassium channels and their evolving gates. Nature. 1994 Sep 8;371(6493):119–122. doi: 10.1038/371119a0. [DOI] [PubMed] [Google Scholar]
  20. Ketchum K. A., Joiner W. J., Sellers A. J., Kaczmarek L. K., Goldstein S. A. A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature. 1995 Aug 24;376(6542):690–695. doi: 10.1038/376690a0. [DOI] [PubMed] [Google Scholar]
  21. Kofuji P., Davidson N., Lester H. A. Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6542–6546. doi: 10.1073/pnas.92.14.6542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Koh D. S., Jonas P., Bräu M. E., Vogel W. A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve. J Membr Biol. 1992 Nov;130(2):149–162. doi: 10.1007/BF00231893. [DOI] [PubMed] [Google Scholar]
  23. Krapivinsky G., Gordon E. A., Wickman K., Velimirović B., Krapivinsky L., Clapham D. E. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. Nature. 1995 Mar 9;374(6518):135–141. doi: 10.1038/374135a0. [DOI] [PubMed] [Google Scholar]
  24. Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J. M., Plowman G. D., Rudy B., Schlessinger J. Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature. 1995 Aug 31;376(6543):737–745. doi: 10.1038/376737a0. [DOI] [PubMed] [Google Scholar]
  25. Levitan I. B. Modulation of ion channels by protein phosphorylation and dephosphorylation. Annu Rev Physiol. 1994;56:193–212. doi: 10.1146/annurev.ph.56.030194.001205. [DOI] [PubMed] [Google Scholar]
  26. Lewis R. S., Cahalan M. D. Potassium and calcium channels in lymphocytes. Annu Rev Immunol. 1995;13:623–653. doi: 10.1146/annurev.iy.13.040195.003203. [DOI] [PubMed] [Google Scholar]
  27. Lingueglia E., Renard S., Waldmann R., Voilley N., Champigny G., Plass H., Lazdunski M., Barbry P. Different homologous subunits of the amiloride-sensitive Na+ channel are differently regulated by aldosterone. J Biol Chem. 1994 May 13;269(19):13736–13739. [PubMed] [Google Scholar]
  28. Lingueglia E., Voilley N., Waldmann R., Lazdunski M., Barbry P. Expression cloning of an epithelial amiloride-sensitive Na+ channel. A new channel type with homologies to Caenorhabditis elegans degenerins. FEBS Lett. 1993 Feb 22;318(1):95–99. doi: 10.1016/0014-5793(93)81336-x. [DOI] [PubMed] [Google Scholar]
  29. Logothetis D. E., Movahedi S., Satler C., Lindpaintner K., Nadal-Ginard B. Incremental reductions of positive charge within the S4 region of a voltage-gated K+ channel result in corresponding decreases in gating charge. Neuron. 1992 Mar;8(3):531–540. doi: 10.1016/0896-6273(92)90281-h. [DOI] [PubMed] [Google Scholar]
  30. Lu Z., MacKinnon R. Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel. Nature. 1994 Sep 15;371(6494):243–246. doi: 10.1038/371243a0. [DOI] [PubMed] [Google Scholar]
  31. MacKinnon R. Pore loops: an emerging theme in ion channel structure. Neuron. 1995 May;14(5):889–892. doi: 10.1016/0896-6273(95)90327-5. [DOI] [PubMed] [Google Scholar]
  32. Matsuda H. Magnesium gating of the inwardly rectifying K+ channel. Annu Rev Physiol. 1991;53:289–298. doi: 10.1146/annurev.ph.53.030191.001445. [DOI] [PubMed] [Google Scholar]
  33. Nichols C. G., Ho K., Hebert S. Mg(2+)-dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes. J Physiol. 1994 May 1;476(3):399–409. doi: 10.1113/jphysiol.1994.sp020141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pascual J. M., Shieh C. C., Kirsch G. E., Brown A. M. K+ pore structure revealed by reporter cysteines at inner and outer surfaces. Neuron. 1995 May;14(5):1055–1063. doi: 10.1016/0896-6273(95)90344-5. [DOI] [PubMed] [Google Scholar]
  35. Pongs O. Molecular biology of voltage-dependent potassium channels. Physiol Rev. 1992 Oct;72(4 Suppl):S69–S88. doi: 10.1152/physrev.1992.72.suppl_4.S69. [DOI] [PubMed] [Google Scholar]
  36. Pongs O. Structure-function studies on the pore of potassium channels. J Membr Biol. 1993 Oct;136(1):1–8. doi: 10.1007/BF00241484. [DOI] [PubMed] [Google Scholar]
  37. Rettig J., Heinemann S. H., Wunder F., Lorra C., Parcej D. N., Dolly J. O., Pongs O. Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit. Nature. 1994 May 26;369(6478):289–294. doi: 10.1038/369289a0. [DOI] [PubMed] [Google Scholar]
  38. Rudy B. Diversity and ubiquity of K channels. Neuroscience. 1988 Jun;25(3):729–749. doi: 10.1016/0306-4522(88)90033-4. [DOI] [PubMed] [Google Scholar]
  39. Salkoff L., Baker K., Butler A., Covarrubias M., Pak M. D., Wei A. An essential 'set' of K+ channels conserved in flies, mice and humans. Trends Neurosci. 1992 May;15(5):161–166. doi: 10.1016/0166-2236(92)90165-5. [DOI] [PubMed] [Google Scholar]
  40. Seeburg P. H. The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 1993 Sep;16(9):359–365. doi: 10.1016/0166-2236(93)90093-2. [DOI] [PubMed] [Google Scholar]
  41. Yang J., Jan Y. N., Jan L. Y. Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel. Neuron. 1995 May;14(5):1047–1054. doi: 10.1016/0896-6273(95)90343-7. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES