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The sodium bicarbonate cotransporter NBCn1 is an electroneutral transporter with a channel activity that conducts Na+ in a HCO3--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 CO2/HCO3-, 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 CO2/HCO3-. 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.
Aalkjaer,
Cation-coupled bicarbonate transporters.
2014,
Pubmed
Boron,
Evaluating the role of carbonic anhydrases in the transport of HCO3--related species.
2010,
Pubmed
Choi,
An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel.
2000,
Pubmed
,
Xenbase
Choi,
SLC4A transporters.
2012,
Pubmed
Cooper,
Molecular and functional characterization of the electroneutral Na/HCO3 cotransporter NBCn1 in rat hippocampal neurons.
2005,
Pubmed
,
Xenbase
Cooper,
Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons.
2009,
Pubmed
Cougnon,
Effect of reactive oxygen species on NH4+ permeation in Xenopus laevis oocytes.
2002,
Pubmed
,
Xenbase
Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed
George,
Bidirectional influence of sodium channel activation on NMDA receptor-dependent cerebrocortical neuron structural plasticity.
2012,
Pubmed
Grichtchenko,
Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger.
2001,
Pubmed
,
Xenbase
Kim,
PDZ domain proteins of synapses.
2004,
Pubmed
Ko,
A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis.
2002,
Pubmed
Lee,
Systematic family-wide analysis of sodium bicarbonate cotransporter NBCn1/SLC4A7 interactions with PDZ scaffold proteins.
2014,
Pubmed
,
Xenbase
Lee,
PSD-95 interacts with NBCn1 and enhances channel-like activity without affecting Na/HCO(3) cotransport.
2012,
Pubmed
,
Xenbase
Lee,
Sodium-bicarbonate cotransporter NBCn1/Slc4a7 inhibits NH4Cl-mediated inward current in Xenopus oocytes.
2011,
Pubmed
,
Xenbase
Lin,
Postsynaptic density protein-95 regulates NMDA channel gating and surface expression.
2004,
Pubmed
,
Xenbase
Low,
Molecular determinants of coordinated proton and zinc inhibition of N-methyl-D-aspartate NR1/NR2A receptors.
2000,
Pubmed
,
Xenbase
Park,
Neuronal expression of sodium/bicarbonate cotransporter NBCn1 (SLC4A7) and its response to chronic metabolic acidosis.
2010,
Pubmed
Park,
Deletion of the Na/HCO3 Transporter NBCn1 Protects Hippocampal Neurons from NMDA-induced Seizures and Neurotoxicity in Mice.
2019,
Pubmed
Park,
Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms.
2017,
Pubmed
,
Xenbase
Parker,
The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.
2013,
Pubmed
Parker,
Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity.
2008,
Pubmed
,
Xenbase
Ren,
Sodium leak channels in neuronal excitability and rhythmic behaviors.
2011,
Pubmed
Richter,
The recruitment of membrane-bound mRNAs for translation in microinjected Xenopus oocytes.
1983,
Pubmed
,
Xenbase
Romero,
The SLC4 family of bicarbonate (HCO₃⁻) transporters.
2013,
Pubmed
Romero,
Cloning and characterization of a Na+-driven anion exchanger (NDAE1). A new bicarbonate transporter.
2000,
Pubmed
,
Xenbase
Salter,
Src kinases: a hub for NMDA receptor regulation.
2004,
Pubmed
Sato,
Purification and characterization of a Src-related p57 protein-tyrosine kinase from Xenopus oocytes. Isolation of an inactive form of the enzyme and its activation and translocation upon fertilization.
1996,
Pubmed
,
Xenbase
Schank,
Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1.
2020,
Pubmed
Shcheynikov,
The Slc26a4 transporter functions as an electroneutral Cl-/I-/HCO3- exchanger: role of Slc26a4 and Slc26a6 in I- and HCO3- secretion and in regulation of CFTR in the parotid duct.
2008,
Pubmed
,
Xenbase
Soleimani,
Ionic mechanism of Na+-HCO3- cotransport in rabbit renal basolateral membrane vesicles.
1989,
Pubmed
Spanagel,
Alcoholism: a systems approach from molecular physiology to addictive behavior.
2009,
Pubmed
Sugrue,
Immunocytochemical localization of the neuron-specific form of the c-src gene product, pp60c-src(+), in rat brain.
1990,
Pubmed
Tauskela,
Protection of cortical neurons against oxygen-glucose deprivation and N-methyl-D-aspartate by DIDS and SITS.
2003,
Pubmed
Traynelis,
Glutamate receptor ion channels: structure, regulation, and function.
2010,
Pubmed
Wang,
Role of Glutamate and NMDA Receptors in Alzheimer's Disease.
2017,
Pubmed
Yu,
Gain control of NMDA-receptor currents by intracellular sodium.
1998,
Pubmed
Yu,
The Role of Intracellular Sodium in the Regulation of NMDA-Receptor-Mediated Channel Activity and Toxicity.
2006,
Pubmed
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
Zhang,
Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors.
2018,
Pubmed
,
Xenbase
Zhekova,
Identification of multiple substrate binding sites in SLC4 transporters in the outward-facing conformation: Insights into the transport mechanism.
2021,
Pubmed
de Lera Ruiz,
Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications.
2015,
Pubmed
