The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The Inhibition of TREK2 Channel by an Oxidizing Agent, 5,5'-dithiobis (2-nitrobenzoic acid), via Interaction with the C-terminus Distal to the 353rd Amino Acid

  • Park, Kyoung-Sun (Division of Molecular and Life Sciences, Hanyang University) ;
  • Bang, Hyo-Weon (Department of Physiology, Chung-Ang University College of Medicine) ;
  • Shin, Eun-Young (Departments of Biochemistry, College of Medicine, Chungbuk National University) ;
  • Kim, Chan-Hyung (Departments of Pharmacology, College of Medicine, Chungbuk National University) ;
  • Kim, Yang-Mi (Departments of physiology, College of Medicine, Chungbuk National University)
  • Published : 2008.08.31
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Abstract

TREK (TWIK-RElated $K^+$ channels) and TRAAK (TWIK-Related Arachidonic acid Activated $K^+$ channels) were expressed in COS-7 cells, and the channel activities were recorded from inside-out membrane patches using holding potential of - 40 mV in symmetrical 150 mM $K^+$ solution. Intracellular application of an oxidizing agent, 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB), markedly decreased the activity of the TREK2, and the activity was partially reversed by the reducing agent, dithiothreitol (DTT). In order to examine the possibility that the target sites for the oxidizing agents might be located in the C-terminus of TREK2, two chimeras were constructed: TREK2 (1-383)/TASK3C and TREK2 (1-353)/TASK3C. The channel activity in the TREK2 (1-383)/TASK3C chimera was still inhibited by DTNB, but not in the TREK2 (1-353)/TASK3C chimera. These results indicate that TREK2 is inhibited by oxidation, and that the target site for oxidation is located between the amino acid residues 353 and 383 in the C-terminus of the TREK2 protein.

Keywords

References

  1. Bang H, Kim Y, Kim D. TREK-2, a new member of the mechanosensitive tandem-pore $K^+$ channel family. J Biol Chem 275: 17412-17419, 2000 https://doi.org/10.1074/jbc.M000445200
  2. Buckler KJ, Honore E. The lipid-activated two-pore domain $K^+$ channel TREK-1 is resistant to hypoxia: implication for ischaemic neuroprotection. J Physiol 562(Pt 1): 213-222, 2005 https://doi.org/10.1113/jphysiol.2004.077503
  3. Caley AJ, Gruss M, Franks NP. The effects of hypoxia on the modulation of human TREK-1 potassium channels. J Physiol 562(Pt 1): 205-212, 2005 https://doi.org/10.1113/jphysiol.2004.076240
  4. DiChiara TJ, Reinhart PH. Redox modulation of hslo $Ca^2+$-activated $K^+$ channels. J Neurosci 17: 4942-4955, 1997 https://doi.org/10.1523/JNEUROSCI.17-13-04942.1997
  5. Haarmann CS, Fink RH, Dulhunty AF. Oxidation and reduction of pig skeletal muscle ryanodine receptors. Biophys J 77: 3010-3022, 1999 https://doi.org/10.1016/S0006-3495(99)77132-8
  6. Honore E. The neuronal background $K_2p$ channels: focus on TREK1. Nat Rev Neurosci 8: 251-261, 2007
  7. Honore E, Maingret F, Lazdunski M, Patel AJ. An intracellular proton sensor commands lipid- and mechano-gating of the $K^+$ channel TREK-1. Embo J 21: 2968-2976, 2002 https://doi.org/10.1093/emboj/cdf288
  8. Kim D. Physiology and pharmacology of two-pore domain potassium channels. Curr Pharm Des 11: 2717-2736, 2005 https://doi.org/10.2174/1381612054546824
  9. Kim Y, Bang H, Gnatenco C, Kim D. Synergistic interaction and the role of C-terminus in the activation of TRAAK $K^+$ channels by pressure, free fatty acids and alkali. Pflugers Arch 442: 64-72, 2001a https://doi.org/10.1007/s004240000496
  10. Kim Y, Gnatenco C, Bang H, Kim D. Localization of TREK-2 $K^+$ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and $pH_i$. Pflugers Arch 442: 952-960, 2001b https://doi.org/10.1007/s004240100626
  11. Kim Y, Lee SH, Ho WK. Hydrogen peroxide selectively increases TREK-2 currents via myosin light chain kinases. Front Biosci 12: 1642-1650, 2007 https://doi.org/10.2741/2176
  12. Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, Honore E. TREK-1 is a heat-activated background $K^+$ channel. Embo J 19: 2483-2491, 2000 https://doi.org/10.1093/emboj/19.11.2483
  13. Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E. Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274: 26691-26696, 1999 https://doi.org/10.1074/jbc.274.38.26691
  14. Miller P, Kemp PJ, Lewis A, Chapman CG, Meadows HJ, Peers C. Acute hypoxia occludes hTREK-1 modulation: re-evaluation of the potential role of tandem P domain $K^+$ channels in central neuroprotection. J Physiol 548(Pt 1): 31-37, 2003
  15. Miller P, Kemp PJ, Peers C. Structural requirements for $O_2$ sensing by the human tandem-P domain channel, hTREK1. Biochem Biophys Res Commun 331: 1253-1256, 2005 https://doi.org/10.1016/j.bbrc.2005.04.042
  16. Miller P, Peers C, Kemp PJ. Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: physiological impact in acidosis and alkalosis. Am J Physiol Cell Physiol 286: C272-282, 2004 https://doi.org/10.1152/ajpcell.00334.2003
  17. Patel AJ, Honore E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M. A mammalian two pore domain mechano-gated S-like $K^+$ channel. Embo J 17: 4283-4290, 1998 https://doi.org/10.1093/emboj/17.15.4283
  18. Ruppersberg JP, Fakler B. Complexity of the regulation of Kir2.1 $K^+$ channels. Neuropharmacology 35: 887-893, 1996 https://doi.org/10.1016/0028-3908(96)00092-5
  19. Ruppersberg JP, Stocker M, Pongs O, Heinemann SH, Frank R, Koenen M. Regulation of fast inactivation of cloned mammalian IKA channels by cysteine oxidation. Nature 352: 711-714, 1991 https://doi.org/10.1038/352711a0
  20. Sullivan JM, Traynelis SF, Chen HS, Escobar W, Heinemann SF, Lipton SA. Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor. Neuron 13: 929-936, 1994 https://doi.org/10.1016/0896-6273(94)90258-5
  21. Tang XD, Daggett H, Hanner M, Garcia ML, McManus OB, Brot N, Weissbach H, Heinemann SH, Hoshi T. Oxidative regulation of large conductance calcium-activated potassium channels. J Gen Physiol 117: 253-274, 2001 https://doi.org/10.1085/jgp.117.3.253
  22. Zeidner G, Sadja R, Reuveny E. Redox-dependent gating of G protein-coupled inwardly rectifying $K^+$ channels. J Biol Chem 276: 35564-35570, 2001 https://doi.org/10.1074/jbc.M105189200