title: A rapid facilitation of acid-sensing ion channels current by corticosterone in cultured hippocampal neurons.
abstract: Acid-sensing ion channels (ASIC) play an important role in the central neuronal system and excessive activation of ASICs induces neuronal damage. Recent studies show that ASIC1a, a subunit of ASIC, is involved in stress processes but the mechanisms by which ASIC1a is regulated by corticosterone (CORT), a stress-induced hormone, are as yet unelucidated. In the present study, to explore the effects of CORT on ASIC1a in cultured hippocampal neurons, the whole-cell patch clamp technique was used. We present data showing that extracellular application of 1 and 10 μM CORT increase the inward current when solution of pH 6.0 is applied to the exterior of the cell. Moreover, extracellular application of membrane-impermeable CORT-BSA (1 μM) maintains current elevation induced by the action of ASIC1a. However, intracellular application of CORT (1 μM) did not increase ASIC1a current. Subsequent extracellular application of CORT enhanced the amplitude of ASIC1a current. Also, RU38486 (10 μM), an antagonist of nuclear glucocorticoids receptor, did not block an increase of ASIC1a current induced by CORT. In addition, CORT application further resulted in a significant enhancement of ASIC1a current in the presence of phorbol 12-myristate 13-acetate (0.5 μM) or bryostatin1 (1 μM), which are both protein kinase C (PKC) agonists. On the contrary, after pretreatment with GF109203X (3 μM), an antagonist of PKC, CORT did not elevate ASIC1a current. These data indicate that the rapid increase of ASIC1a current induced by CORT may be caused by the activation of corticosteroid receptors found on the cell membranes of hippocampal neurons and it may involve a PKC-dependent mechanism.
authors: Medical College, Jianghan University, Wuhan, 430056, China.
authors: Zhe
authors: Z
authors: Xiong
authors: Yan
authors: Y
authors: Liu
authors: Lian
authors: L
authors: Hu
authors: BaoMiao
authors: B
authors: Ma
authors: YongXun
authors: Y
authors: Ai
authors: ChengLiang
authors: C
authors: Xiong
mesh_terms: D062565:Acid Sensing Ion Channels / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D062565:Acid Sensing Ion Channels; D011493:Protein Kinase C; D003345:Corticosterone
references: J Physiol. 2002 Mar 1;539(Pt 2):485-94
references: 11882680
references: PLoS One. 2012;7(4):e34124
references: 22509272
references: Behav Brain Res. 2012 Apr 21;230(1):167-74
references: 22327185
references: Psychopharmacology (Berl). 2009 Mar;203(1):41-52
references: 18949460
references: Biochim Biophys Acta. 2003 Feb 17;1619(3):301-16
references: 12573490
references: Brain Res. 2004 Aug 13;1017(1-2):197-207
references: 15261115
references: J Physiol. 2012 Apr 1;590(7):1535-46
references: 22331421
references: J Neurophysiol. 2008 Feb;99(2):426-41
references: 18094106
references: J Neurochem. 2002 Dec;83(6):1441-51
references: 12472898
references: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4459-64
references: 18334630
references: Neuron. 2000 Apr;26(1):133-41
references: 10798398
references: Neuron. 2002 Apr 25;34(3):463-77
references: 11988176
references: Eur J Pharmacol. 2007 Sep 10;570(1-3):43-9
references: 17610871
references: Biol Psychiatry. 2012 Sep 15;72(6):491-8
references: 22521150
references: J Biol Chem. 2010 Feb 26;285(9):6101-8
references: 20051515
references: J Physiol. 2003 Jan 1;546(Pt 1):77-87
references: 12509480
references: J Neurosci. 1998 Apr 1;18(7):2685-96
references: 9502826
references: Biochem J. 2002 Feb 1;361(Pt 3):443-50
references: 11802773
references: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3621-6
references: 14988500
references: Neuroendocrinology. 2011;94(4):278-90
references: 22024815
references: J Neurosci. 2004 Oct 6;24(40):8678-89
references: 15470133
references: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16556-61
references: 17060608
references: Mol Neurodegener. 2013 Jan 17;8:3
references: 23327202
references: Biochem Biophys Res Commun. 2004 Aug 20;321(2):510-3
references: 15358205
references: J Biol Chem. 2002 Feb 15;277(7):5203-8
references: 11739374
references: Brain Res. 1995 Aug 28;690(1):41-7
references: 7496805
references: Am J Physiol Cell Physiol. 2010 Dec;299(6):C1355-62
references: 20826761
references: Trends Neurosci. 2003 Sep;26(9):477-83
references: 12948658
references: Acta Histochem Cytochem. 2006 Dec 28;39(6):173-81
references: 17327904
references: Neuroscience. 2007 Mar 16;145(2):631-41
references: 17224241
references: Neuroreport. 2000 Jul 14;11(10):2217-22
references: 10923674
references: J Chem Neuroanat. 2009 Dec;38(4):266-72
references: 19505571
references: Neuron. 2012 Mar 8;73(5):962-77
references: 22405206
references: Int J Dev Neurosci. 2011 May;29(3):215-23
references: 21345366
references: J Neurosci. 2009 Apr 29;29(17):5381-8
references: 19403806