The sodium-bicarbonate cotransporter NBCe1 supports glutamine efflux via SNAT3 (SLC38A3) co-expressed in Xenopus oocytes

Wendel, Christina; Becker, Holger M.; Deitmer, Joachim W.

doi:10.1007/s00424-007-0351-y

Cited by 7 publications

(3 citation statements)

References 28 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For measurement of intracellular pH (pH i ) and membrane potential, double-, and for intracellular Na + (Na + i ), single-barreled microelectrodes were used; the manufacture and application have been described in detail previously [31], [32]. Briefly, for double-barreled microelectrodes, two borosilicate glass capillaries of 1.0 and 1.5 mm in diameter were twisted together and pulled to a micropipette.…”

Section: Methodsmentioning

confidence: 99%

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

et al. 2011

Self Cite

View full text Add to dashboard Cite

Transport metabolons have been discussed between carbonic anhydrase II (CAII) and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1), to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM), while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity.

show abstract

Section: Methodsmentioning

confidence: 99%

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…Consistent with the downregulation of NBCe1, acute hypoxia inhibits electrogenic Na,HCO 3 -cotransport activity in hippocampal astrocytes (25). In addition, recent studies show that NBCe1 activity enhances glutamine efflux via the glutamine transporter SLC38A3 (335) and fast glycolysis in response to excitatory synaptic transmission (274). …”

Section: The Postcloning Eramentioning

confidence: 99%

Cation‐Coupled Bicarbonate Transporters

Aalkjær

Boedtkjer

Choi

et al. 2014

Comprehensive Physiology

View full text Add to dashboard Cite

Cation-coupled HCO3− transport was initially identified in the mid-1970s when pioneering studies showed that acid extrusion from cells is stimulated by CO2/HCO3− and associated with Na+ and Cl− movement. The first Na+-coupled bicarbonate transporter (NCBT) was expression-cloned in the late 1990s. There are currently five mammalian NCBTs in the SLC4-family: the electrogenic Na,HCO3-cotransporters NBCe1 and NBCe2 (SLC4A4 and SLC4A5 gene products); the electroneutral Na,HCO3-cotransporter NBCn1 (SLC4A7 gene product); the Na+-driven Cl,HCO3-exchanger NDCBE (SLC4A8 gene product); and NBCn2/NCBE (SLC4A10 gene product), which has been characterized as an electroneutral Na,HCO3-cotransporter or a Na+-driven Cl,HCO3-exchanger. Despite the similarity in amino acid sequence and predicted structure among the NCBTs of the SLC4-family, they exhibit distinct differences in ion dependency, transport function, pharmacological properties, and interactions with other proteins. In epithelia, NCBTs are involved in transcellular movement of acid-base equivalents and intracellular pH control. In nonepithelial tissues, NCBTs contribute to intracellular pH regulation; and hence, they are crucial for diverse tissue functions including neuronal discharge, sensory neuron development, performance of the heart, and vascular tone regulation. The function and expression levels of the NCBTs are generally sensitive to intracellular and systemic pH. Animal models have revealed pathophysiological roles of the transporters in disease states including metabolic acidosis, hypertension, visual defects, and epileptic seizures. Studies are being conducted to understand the physiological consequences of genetic polymorphisms in the SLC4-members, which are associated with cancer, hypertension, and drug addiction. Here, we describe the current knowledge regarding the function, structure, and regulation of the mammalian cation-coupled HCO3− transporters of the SLC4-family.

show abstract

“…Astroglial HCO 3 – secretion contributes to the maintenance of pH e within the physiological window, and thus is fundamental for the control of H + -dependent neuronal excitability (Deitmer, 1992; Chesler, 2003; Theparambil et al, 2017). The secretion of HCO 3 – via NBCe1 (Deitmer, 1991) could also facilitate shuttling of H + -coupled substrates, like lactate and glutamine, to the brain extracellular spaces, since co-transported H + is effectively buffered by HCO 3 – (Becker and Deitmer, 2004; Becker et al, 2004; Wendel et al, 2008). Astrocytes are also reported to express HCO 3 – -independent pH regulators, like the Na + /H + exchanger NHE1 and vacuolar type ATPase (V-ATPase) (Chesler, 2003; Hansen et al, 2015).…”

Section: Ph Regulation In Astrocytesmentioning

confidence: 99%

Energy Dynamics in the Brain: Contributions of Astrocytes to Metabolism and pH Homeostasis

et al. 2019

Self Cite

View full text Add to dashboard Cite

Regulation of metabolism is complex and involves enzymes and membrane transporters, which form networks to support energy dynamics. Lactate, as a metabolic intermediate from glucose or glycogen breakdown, appears to play a major role as additional energetic substrate, which is shuttled between glycolytic and oxidative cells, both under hypoxic and normoxic conditions. Transport of lactate across the cell membrane is mediated by monocarboxylate transporters (MCTs) in cotransport with H+, which is a substrate, a signal and a modulator of metabolic processes. MCTs form a “transport metabolon” with carbonic anhydrases (CAs), which not only provide a rapid equilibrium between CO2, HCO3– and H+, but, in addition, enhances lactate transport, as found in Xenopus oocytes, employed as heterologous expression system, as well as in astrocytes and cancer cells. Functional interactions between different CA isoforms and MCTs have been found to be isoform-specific, independent of the enzyme’s catalytic activity, and they require physical interaction between the proteins. CAs mediate between different states of metabolic acidosis, induced by glycolysis and oxidative phosphorylation, and play a relay function in coupling pH regulation and metabolism. In the brain, metabolic processes in astrocytes appear to be linked to bicarbonate transport and to neuronal activity. Here, we focus on physiological processes of energy dynamics in astrocytes as well as on the transfer of energetic substrates to neurons.

show abstract

The sodium-bicarbonate cotransporter NBCe1 supports glutamine efflux via SNAT3 (SLC38A3) co-expressed in Xenopus oocytes

Cited by 7 publications

References 28 publications

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

Cation‐Coupled Bicarbonate Transporters

Energy Dynamics in the Brain: Contributions of Astrocytes to Metabolism and pH Homeostasis

Contact Info

Product

Resources

About