Bocker, Hartmut T., Heinrich, Theresa, Liebmann, Lutz, Hennings, J. Christopher, Seemann, Eric, Gerth, Melanie, Jakovcevski, Igor, Preobraschenski, Julia, Kessels, Michael M., Westermann, Martin, Isbrandt, Dirk, Jahn, Reinhard, Qualmann, Britta and Huebner, Christian A. (2019). The Na+/H+ Exchanger Nhe1 Modulates Network Excitability via GABA Release. Cereb. Cortex, 29 (10). S. 4263 - 4277. CARY: OXFORD UNIV PRESS INC. ISSN 1460-2199

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Abstract

Brain functions are extremely sensitive to pH changes because of the pH-dependence of proteins involved in neuronal excitability and synaptic transmission. Here, we show that the Na+/H+ exchanger Nhe1, which uses the Na+ gradient to extrude H+, is expressed at both inhibitory and excitatory presynapses. We disrupted Nhe1 specifically in mice either in Emx1- positive glutamatergic neurons or in parvalbumin-positive cells, mainly GABAergic interneurons. While Nhe1 disruption in excitatory neurons had no effect on overall network excitability, mice with disruption of Nhe1 in parvalbumin-positive neurons displayed epileptic activity. From our electrophysiological analyses in the CA1 of the hippocampus, we conclude that the disruption in parvalbumin-positive neurons impairs the release of GABA-loaded vesicles, but increases the size of GABA quanta. The latter is most likely an indirect pH-dependent effect, as Nhe1 was not expressed in purified synaptic vesicles itself. Conclusively, our data provide first evidence that Nhe1 affects network excitability via modulation of inhibitory interneurons.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bocker, Hartmut T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinrich, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liebmann, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hennings, J. ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seemann, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerth, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakovcevski, IgorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preobraschenski, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kessels, Michael M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westermann, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isbrandt, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jahn, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qualmann, BrittaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebner, Christian A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-132157
DOI: 10.1093/cercor/bhy308
Journal or Publication Title: Cereb. Cortex
Volume: 29
Number: 10
Page Range: S. 4263 - 4277
Date: 2019
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1460-2199
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PRESYNAPTIC NERVE-TERMINALS; TARGETED DISRUPTION; INTRACELLULAR PH; PLASMA-MEMBRANE; CYTOSOLIC PH; INTERNEURONS; RECEPTORS; NEURONS; IDENTIFICATION; CYTOSKELETONMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13215

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