Abstract
Two-pore domain K+ channels are widely expressed in many types of cells, and have various important functions, especially maintaining the resting membrane potential. In the previous report, we have confirmed the presence of several kinds of two-pore domain K+ channels in the periodontal ligament (PDL) fibroblasts. It is well known that dexamethasone (Dex) regulates the functions of various kinds of ion channels. In this work, we investigate if Dex affects the gene expressions of the two-pore domain K+ channels in the PDL fibroblasts. We also examined the effects of other steroid hormones on the K+ channels gene expression. The mRNA levels of two-pore domain K+ channels in human PDL fibroblasts were examined in the presence or absence of Dex by RT-PCR. The effects of other steroid hormones (aldosterone, estrogen, 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and retinoic acid) were also examined. Dex significantly induced the expression of TASK-1 and TWIK-2 in mRNA levels in both a dose- and a time-dependent manner. The stimulatory effects of Dex were completely abolished by a glucocorticoid receptor antagonist. 1,25-(OH)2D3 also increased the TASK-1 mRNA levels but had no effect on TWIK-2 expression. Dex, one of the potent glucocorticoid, probably have a protective role against external stimuli by maintaining the membrane potential of PDL fibroblasts through the up-regulation of TASK-1 and TWIK-2 K+ channels.
Similar content being viewed by others
References
Arcari P.; Martinelli R.; Salvatore F. The complete sequence of a full length cDNA for human liver glyceraldehyde-3-phosphate dehydrogenase: evidence for multiple mRNA species. Nucleic Acids Res. 12(23): 9179–9189; 1984.
BenMohamed F.; Ferron L.; Ruchon Y.; Gouadon E.; Renaud J. F.; Capuano V. Regulation of T-type Cav3.1 channels expression by synthetic glucocorticoid dexamethasone in neonatal cardiac myocytes. Mol Cell Biochem 320(1-2): 173–183; 2009.
Buckingham S. D.; Kidd J. F.; Law R. J.; Franks C. J.; Sattelle D. B. Structure and function of two-pore-domain K+ channels: contributions from genetic model organisms. Trends Pharmacol Sci 26(7): 361–367; 2005.
Byers M. R.; Rafie M. M.; Westenbroek R. E. Dexamethasone effects on Nav1.6 in tooth pulp, dental nerves, and alveolar osteoclasts of adult rats. Cell Tissue Res 338(2): 217–226; 2009.
Carnes D. L.; Maeder C. L.; Graves D. T. Cells with osteoblastic phenotypes can be explanted from human gingiva and periodontal ligament. J Periodontol 68(7): 701–707; 1997.
Chavez R. A.; Gray A. T.; Zhao B. B.; Kindler C. H.; Mazurek M. J.; Mehta Y.; Forsayeth J. R.; Yost C. S. TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family. J Biol Chem 274(12): 7887–7892; 1999.
Duprat F.; Lesage F.; Fink M.; Reyes R.; Heurteaux C.; Lazdunski M. TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J. 16(17): 5464–5471; 1997.
Goldstein S. A.; Bockenhauer D.; O’Kelly I.; Zilberberg N. Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci 2(3): 175–184; 2001.
Hakki S. S.; Hakki E. E.; Nohutcu R. M. Regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by basic fibroblast growth factor and dexamethasone in periodontal ligament cells. J Periodontal Res 44(6): 794–802; 2009.
Hayami T.; Zhang Q.; Kapila Y.; Kapila S. Dexamethasone’s enhancement of osteoblastic markers in human periodontal ligament cells is associated with inhibition of collagenase expression. Bone 40(1): 93–104; 2007.
Holzer P. Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 292(3): 699–705; 2007.
Inglis S. K.; Brown S. G.; Constable M. J.; McTavish N.; Olver R. E.; Wilson S. M. A Ba2+-resistant, acid-sensitive K+ conductance in Na+-absorbing H441 human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 292(5): 1304–1312; 2007.
Kim D.; Fujita A.; Horio Y.; Kurachi Y. Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ. Res. 82(4): 513–518; 1998.
Kindler C. H.; Yost C. S. Two-pore domain potassium channels: new sites of local anesthetic action and toxicity. Reg Anesth Pain Med 30(3): 260–274; 2005.
Kindler C. H.; Yost C. S.; Gray A. T. Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem. Anesthesiology 90(4): 1092–1102; 1999.
Leonoudakis D.; Gray A. T.; Winegar B. D.; Kindler C. H.; Harada M.; Taylor D. M.; Chavez R. A.; Forsayeth J. R.; Yost C. S. An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. J Neurosci 18(3): 868–877; 1998.
Lesage F. Pharmacology of neuronal background potassium channels. Neuropharmacology 44(1): 1–7; 2003.
Lesage F.; Guillemare E.; Fink M.; Duprat F.; Lazdunski M.; Romey G.; Barhanin J. TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 15(5): 1004–1011; 1996.
Lesage F.; Lazdunski M. Molecular and functional properties of two-pore-domain potassium channels. Am. J. Physiol. Ren. Physiol. 279(5): F793–F801; 2000a.
Lesage F.; Maingret F.; Lazdunski M. Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K+ channel. FEBS Lett. 471(2–3): 137–140; 2000b.
Lesage F.; Terrenoire C.; Romey G.; Lazdunski M. Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J. Biol. Chem. 275(37): 28398–28405; 2000c.
Maingret F.; Patel A. J.; Lazdunski M.; Honoré E. The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1. EMBO J 20(1-2): 47–54; 2001.
McTavish N.; Getty J.; Burchell A.; Wilson S. M. Glucocorticoids can activate the α-ENaC gene promoter independently of SGK1. Biochem. J. 423(2): 189–197; 2009.
Medhurst A. D.; Rennie G.; Chapman C. G.; Meadows H.; Duckworth M. D.; Kelsell R. E.; Gloger I. I.; Pangalos M. N. Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Brain Res Mol Brain Res 86(1-2): 101–114; 2001.
Meuth S. G.; Bittner S.; Meuth P.; Simon O. J.; Budde T.; Wiendl H. TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions. J Biol Chem 283(21): 14559–14570; 2008.
Nakajima T.; Jo T.; Meguro K.; Oonuma H.; Ma J.; Kubota N.; Imuta H.; Takano H.; Iida H.; Nagase T.; Nagata T. Effect of dexamethasone on voltage-gated Na+ channel in cultured human bronchial smooth muscle cells. Life Sci. 82(23–24): 1210–1215; 2008.
Nishikawa M.; Yamaguchi Y.; Yoshitake K.; Saeki Y. Effects of TNFα and prostaglandin E2 on the expression of MMPs in human periodontal ligament fibroblasts. J. Periodontal Res. 37(3): 167–176; 2002.
Ogata Y.; Yamauchi M.; Kim R. H.; Li J. J.; Freedman L. P.; Sodek J. Glucocorticoid regulation of bone sialoprotein (BSP) gene expression. Identification of a glucocorticoid response element in the bone sialoprotein gene promoter. Eur J Biochem 230(1): 183–92; 1995.
Ohara A.; Saeki Y.; Nishikawa M.; Yamamoto Y.; Yamamoto G. Single-channel recordings of TREK-1 K+ channels in periodontal ligament fibroblasts. J. Dent. Res. 85(7): 664–669; 2006.
Patel A. J.; Honoré E. Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 24(6): 339–346; 2001.
Patel A. J.; Honoré E.; Lesage F.; Fink M.; Romey G.; Lazdunski M. Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2(5): 422–426; 1999.
Patel A. J.; Maingret F.; Magnone V.; Fosset M.; Lazdunski M.; Honoré E. TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem 275(37): 28722–28730; 2000.
Reyes R.; Duprat F.; Lesage F.; Fink M.; Salinas M.; Farman N.; Lazdunski M. Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J. Biol. Chem. 273(47): 30863–30869; 1998.
Roy J. W.; Cowley E. A.; Blay J.; Linsdell P. The intermediate conductance Ca2+-activated K+ channel inhibitor TRAM-34 stimulates proliferation of breast cancer cells via activation of oestrogen receptors. Br J Pharmacol 159(3): 650–658; 2010.
Saeki Y.; Ohara A.; Nishikawa M.; Yamamoto T.; Yamamoto G. The presence of arachidonic acid-activated K+ channel, TREK-1, in human periodontal ligament fibroblasts. Drug Metab. Rev. 39(2–3): 457–465; 2007.
Sanders K. M.; Koh S. D. Two-pore-domain potassium channels in smooth muscles: new components of myogenic regulation. J Physiol 570(Pt 1): 37–43; 2006.
Sano Y.; Inamura K.; Miyake A.; Mochizuki S.; Kitada C.; Yokoi H.; Nozawa K.; Okada H.; Matsushime H.; Furuichi K. A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. J. Biol. Chem. 278(30): 27406–27412; 2003.
Sirois J. E.; Lei Q.; Talley E. M.; Lynch C.; Bayliss D. A. The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics. J Neurosci 20(17): 6347–6354; 2000.
Son E. J.; Kim S. H.; Park H. Y.; Kim S. J.; Yoon J. H.; Chung H. P.; Choi J. Y. Activation of epithelial sodium channel in human middle ear epithelial cells by dexamethasone. Eur J Pharmacol 602(2-3): 383–387; 2009.
Talley E. M.; Solorzano G.; Lei Q.; Kim D.; Bayliss D. A. Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci 21(19): 7491–7505; 2001.
Wei Y.; Zhang C.; Miao X.; Xing F.; Liu X.; Zhao H.; Zhan X.; Han D. Effects of glucocorticoid on cyclic nucleotide-gated channels of olfactory receptor neurons. J. Otolaryngol. Head Neck Surg. 38(1): 90–95; 2009.
Author information
Authors and Affiliations
Corresponding author
Additional information
Editor: J. Denry Sato
Rights and permissions
About this article
Cite this article
Yamamoto, T., Ohara, A., Nishikawa, M. et al. Dexamethasone-induced up-regulation of two-pore domain K+ channel genes, TASK-1 and TWIK-2, in cultured human periodontal ligament fibroblasts. In Vitro Cell.Dev.Biol.-Animal 47, 273–279 (2011). https://doi.org/10.1007/s11626-011-9388-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11626-011-9388-5