Cargando…
Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function
The sodium bicarbonate cotransporter NBCn1 is an electroneutral transporter with a channel activity that conducts Na(+) in a HCO(3)(–)-independent manner. This channel activity was suggested to functionally affect other membrane proteins which permeate Na(+) influx. We previously reported that NBCn1...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947554/ https://www.ncbi.nlm.nih.gov/pubmed/35723309 http://dx.doi.org/10.3390/cimb44030086 |
_version_ | 1784674467423715328 |
---|---|
author | Choi, Inyeong Yang, Hansoo Kim, Eunjin Lee, Soojung |
author_facet | Choi, Inyeong Yang, Hansoo Kim, Eunjin Lee, Soojung |
author_sort | Choi, Inyeong |
collection | PubMed |
description | The sodium bicarbonate cotransporter NBCn1 is an electroneutral transporter with a channel activity that conducts Na(+) in a HCO(3)(–)-independent manner. This channel activity was suggested to functionally affect other membrane proteins which permeate Na(+) influx. We previously reported that NBCn1 is associated with the NMDA receptors (NMDARs) at the molecular and physiological levels. In this study, we examined whether NBCn1 channel activity affects NMDAR currents and whether this effect involves the interaction between the two proteins. NBCn1 and the NMDAR subunits GluN1A/GluN2A were expressed in Xenopus oocytes, and glutamate currents produced by the receptors were measured using two-electrode voltage clamp. In the absence of CO(2)/HCO(3)(–), NBCn1 channel activity decreased glutamate currents mediated by GluN1A/GluN2A. NBCn1 also decreased the slope of the current–voltage relationships for the glutamate current. Similar effects on the glutamate current were observed with and without PSD95, which can cluster NBCn1 and NMDARs. The channel activity was also observed in the presence of CO(2)/HCO(3)(–). We conclude that NBCn1 channel activity decreases NMDAR function. Given that NBCn1 knockout mice develop a downregulation of NMDARs, our results are unexpected and suggest that NBCn1 has dual effects on NMDARs. It stabilizes NMDAR expression but decreases receptor function by its Na(+) channel activity. The dual effects may play an important role in fine-tuning the regulation of NMDARs in the brain. |
format | Online Article Text |
id | pubmed-8947554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89475542022-06-04 Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function Choi, Inyeong Yang, Hansoo Kim, Eunjin Lee, Soojung Curr Issues Mol Biol Article The sodium bicarbonate cotransporter NBCn1 is an electroneutral transporter with a channel activity that conducts Na(+) in a HCO(3)(–)-independent manner. This channel activity was suggested to functionally affect other membrane proteins which permeate Na(+) influx. We previously reported that NBCn1 is associated with the NMDA receptors (NMDARs) at the molecular and physiological levels. In this study, we examined whether NBCn1 channel activity affects NMDAR currents and whether this effect involves the interaction between the two proteins. NBCn1 and the NMDAR subunits GluN1A/GluN2A were expressed in Xenopus oocytes, and glutamate currents produced by the receptors were measured using two-electrode voltage clamp. In the absence of CO(2)/HCO(3)(–), NBCn1 channel activity decreased glutamate currents mediated by GluN1A/GluN2A. NBCn1 also decreased the slope of the current–voltage relationships for the glutamate current. Similar effects on the glutamate current were observed with and without PSD95, which can cluster NBCn1 and NMDARs. The channel activity was also observed in the presence of CO(2)/HCO(3)(–). We conclude that NBCn1 channel activity decreases NMDAR function. Given that NBCn1 knockout mice develop a downregulation of NMDARs, our results are unexpected and suggest that NBCn1 has dual effects on NMDARs. It stabilizes NMDAR expression but decreases receptor function by its Na(+) channel activity. The dual effects may play an important role in fine-tuning the regulation of NMDARs in the brain. MDPI 2022-03-13 /pmc/articles/PMC8947554/ /pubmed/35723309 http://dx.doi.org/10.3390/cimb44030086 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Choi, Inyeong Yang, Hansoo Kim, Eunjin Lee, Soojung Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function |
title | Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function |
title_full | Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function |
title_fullStr | Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function |
title_full_unstemmed | Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function |
title_short | Bicarbonate-Independent Sodium Conductance of Na/HCO(3) Cotransporter NBCn1 Decreases NMDA Receptor Function |
title_sort | bicarbonate-independent sodium conductance of na/hco(3) cotransporter nbcn1 decreases nmda receptor function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947554/ https://www.ncbi.nlm.nih.gov/pubmed/35723309 http://dx.doi.org/10.3390/cimb44030086 |
work_keys_str_mv | AT choiinyeong bicarbonateindependentsodiumconductanceofnahco3cotransporternbcn1decreasesnmdareceptorfunction AT yanghansoo bicarbonateindependentsodiumconductanceofnahco3cotransporternbcn1decreasesnmdareceptorfunction AT kimeunjin bicarbonateindependentsodiumconductanceofnahco3cotransporternbcn1decreasesnmdareceptorfunction AT leesoojung bicarbonateindependentsodiumconductanceofnahco3cotransporternbcn1decreasesnmdareceptorfunction |