title: Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons.
abstract: Acid-sensing ion channels (ASICs), a member of the degenerin/epithelial Na+ channel superfamily, are widely expressed in the mammalian CNS. Accumulating evidence suggests that ASIC current density is higher in GABAergic interneurons than that in glutamatergic pyramidal neurons (PNs) in the hippocampus. Such differential expression of ASICs in cortical networks is thought to be a key element for seizure termination. However, GABAergic interneurons are highly diverse; it is unclear whether the functional expression of ASICs differs in distinct GABAergic interneuron subtypes. Moreover, the subunit composition of ASICs in individual GABAergic interneurons remains unknown. By combining patch-clamp recording and single-cell reverse transcription (RT)-PCR analysis, we correlated ASIC currents with their gene expression in acute rat hippocampal slices. The results yielded several surprising findings. First, ASIC current density of oriens lacunosum-moleculare (O-LM) cells in the CA1 region, a classical type of dendrite-targeting interneuron, is 6 times greater than that of fast-spiking basket cells (BCs) in the dentate gyrus, a major class of soma-targeting interneuron. Second, the recovery of ASICs from desensitization is slowest in BCs, intermediate in PNs, and fastest in O-LM cells. Third, the tarantula venom psalmotoxin 1, the specific blocker for ASIC1a homomers, inhibits ASIC currents in BCs but not in O-LM cells. Finally, single-cell RT-PCR analysis reveals coexpression of ASIC1a and ASIC2 subunit transcripts in O-LM cells, whereas only ASIC1a subunit transcript is detected in most BCs. Thus, differential expression of ASICs in inhibitory microcircuits likely contributes to the distinct roles of GABAergic interneurons in normal physiology and pathophysiology.
authors.affiliation: Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Ju-Yun
authors.initials: JY
authors.lastname: Weng
authors.forename: Yen-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Lien
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D013111:Spider Venoms; D005680:gamma-Aminobutyric Acid
references.citation: J Physiol. 2003 Jan 1;546(Pt 1):77-87
references.pmid: 12509480
references.citation: J Physiol. 2000 Apr 1;524 Pt 1:91-116
references.pmid: 10747186
references.citation: Neuroscience. 2009 Dec 29;164(4):1701-11
references.pmid: 19782725
references.citation: J Physiol. 1995 Jun 1;485 ( Pt 2):383-402
references.pmid: 7545230
references.citation: J Biol Chem. 2004 Apr 30;279(18):18296-305
references.pmid: 14960591
references.citation: Neuroscience. 2001;108(4):587-600
references.pmid: 11738496
references.citation: J Neurosci. 1998 Oct 15;18(20):8111-25
references.pmid: 9763458
references.citation: Nature. 2003 Feb 20;421(6925):844-8
references.pmid: 12594513
references.citation: Nat Protoc. 2007;2(2):434-48
references.pmid: 17406605
references.citation: Nat Rev Neurosci. 2001 Jan;2(1):11-23
references.pmid: 11253355
references.citation: Neuron. 2005 Nov 23;48(4):635-46
references.pmid: 16301179
references.citation: J Neurosci. 2003 Mar 15;23(6):2058-68
references.pmid: 12657664
references.citation: J Physiol. 2002 Mar 1;539(Pt 2):485-94
references.pmid: 11882680
references.citation: J Gen Physiol. 2005 Jul;126(1):71-9
references.pmid: 15955877
references.citation: J Neurosci. 1996 Jan 15;16(2):506-18
references.pmid: 8551335
references.citation: Pflugers Arch. 1993 Jun;423(5-6):511-8
references.pmid: 8351200
references.citation: Neuroscience. 2002;110(4):723-30
references.pmid: 11934479
references.citation: Nature. 1997 Mar 13;386(6621):173-7
references.pmid: 9062189
references.citation: Neuron. 2003 Jan 9;37(1):75-84
references.pmid: 12526774
references.citation: Trends Neurosci. 2006 Oct;29(10):578-86
references.pmid: 16891000
references.citation: Curr Opin Pharmacol. 2008 Feb;8(1):25-32
references.pmid: 17945532
references.citation: Trends Neurosci. 2004 Aug;27(8):475-81
references.pmid: 15271495
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16556-61
references.pmid: 17060608
references.citation: J Neurosci. 2000 Aug 1;20(15):5594-607
references.pmid: 10908596
references.citation: Nat Rev Neurosci. 2004 Oct;5(10):793-807
references.pmid: 15378039
references.citation: Neuron. 2007 Oct 4;56(1):33-42
references.pmid: 17920013
references.citation: Cell. 2004 Sep 17;118(6):687-98
references.pmid: 15369669
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3245-50
references.pmid: 9501248
references.citation: Nature. 2004 Jun 17;429(6993):717-23
references.pmid: 15170216
references.citation: Nat Neurosci. 2007 Aug;10(8):943-5
references.pmid: 17632507
references.citation: Nat Neurosci. 2001 Jan;4(1):52-62
references.pmid: 11135645
references.citation: Nature. 1995 Nov 2;378(6552):75-8
references.pmid: 7477292
references.citation: Brain. 2005 Jan;128(Pt 1):138-52
references.pmid: 15548550
references.citation: Nat Neurosci. 2008 Jul;11(7):816-22
references.pmid: 18536711
references.citation: J Physiol. 2002 Jan 15;538(Pt 2):405-19
references.pmid: 11790809
references.citation: J Neurophysiol. 2008 Feb;99(2):426-41
references.pmid: 18094106
references.citation: Neuron. 2005 Feb 3;45(3):405-17
references.pmid: 15694327
references.citation: Science. 2008 Jul 4;321(5885):53-7
references.pmid: 18599766
references.citation: J Neurosci. 2010 Jan 27;30(4):1337-47
references.pmid: 20107060
references.citation: J Neurosci. 2009 Jul 1;29(26):8438-46
references.pmid: 19571134
references.citation: J Physiol. 2006 Jul 1;574(Pt 1):229-43
references.pmid: 16690716
references.citation: Epilepsy Res. 1998 Nov;32(3):363-9
references.pmid: 9839776
references.citation: Adv Physiol Educ. 2002 Dec;26(1-4):327-41
references.pmid: 12444005
references.citation: Neuron. 2002 Apr 25;34(3):463-77
references.pmid: 11988176
references.citation: Trends Neurosci. 2004 Jan;27(1):30-40
references.pmid: 14698608
references.citation: J Physiol. 2008 Apr 15;586(8):2061-75
references.pmid: 18276734
references.citation: Neuron. 1996 Apr;16(4):815-23
references.pmid: 8607999
references.citation: Hippocampus. 1996;6(4):347-470
references.pmid: 8915675
references.citation: Biophys J. 2000 Jul;79(1):314-20
references.pmid: 10866957
references.citation: J Neurosci. 2009 Apr 29;29(17):5381-8
references.pmid: 19403806