| First Author | Bocker HT | Year | 2019 |
| Journal | Cereb Cortex | Volume | 29 |
| Issue | 10 | Pages | 4263-4276 |
| PubMed ID | 30541023 | Mgi Jnum | J:342724 |
| Mgi Id | MGI:6878973 | Doi | 10.1093/cercor/bhy308 |
| Citation | Bocker HT, et al. (2019) The Na+/H+ Exchanger Nhe1 Modulates Network Excitability via GABA Release. Cereb Cortex 29(10):4263-4276 |
| abstractText | 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. |
