Synaptic Glutamate Release Is Modulated by the Na+-Driven Cl−/HCO3−Exchanger Slc4a8

Sinning, Anne; Liebmann, Lutz; Kougioumtzes, Alexandra; Westermann, Martin; Bruehl, Claus; Hübner, Christian A.

doi:10.1523/jneurosci.0269-11.2011

Cited by 72 publications

(102 citation statements)

References 66 publications

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“…The neuroprotective role of NBCn1 knockdown in these experiments is consistent with the hypothesis that a reduction in pH i reduces neuronal excitability and is also in accordance with the higher seizure threshold of brain slices from NDCBE and NBCn2 knockout mice (429,889), the enhanced neuronal survival in NHE1-null mice following ischemic injury (614), and the proposed enhancement of neuronal excitability by NBCe1.…”

Section: I) Central Nervous System A) Neuroprotection From Glutamatesupporting

confidence: 87%

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

Parker

Boron

2013

Physiological Reviews

248

262

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The mammalian Slc4 (Solute carrier 4) family of transporters is a functionally diverse group of 10 multi-spanning membrane proteins that includes three Cl-HCO3 exchangers (AE1-3), five Na(+)-coupled HCO3(-) transporters (NCBTs), and two other unusual members (AE4, BTR1). In this review, we mainly focus on the five mammalian NCBTs-NBCe1, NBCe2, NBCn1, NDCBE, and NBCn2. Each plays a specialized role in maintaining intracellular pH and, by contributing to the movement of HCO3(-) across epithelia, in maintaining whole-body pH and otherwise contributing to epithelial transport. Disruptions involving NCBT genes are linked to blindness, deafness, proximal renal tubular acidosis, mental retardation, and epilepsy. We also review AE1-3, AE4, and BTR1, addressing their relevance to the study of NCBTs. This review draws together recent advances in our understanding of the phylogenetic origins and physiological relevance of NCBTs and their progenitors. Underlying these advances is progress in such diverse disciplines as physiology, molecular biology, genetics, immunocytochemistry, proteomics, and structural biology. This review highlights the key similarities and differences between individual NCBTs and the genes that encode them and also clarifies the sometimes confusing NCBT nomenclature.

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Section: I) Central Nervous System A) Neuroprotection From Glutamatesupporting

confidence: 87%

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

Parker

Boron

2013

Physiological Reviews

248

262

View full text Add to dashboard Cite

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“…Axon length in 5-day-old spinal cord motor neuron cultures from E12.5 embryos was determined as reported previously (40). Cortical neurons and glia cells were prepared from P0 or P1 animals and cultured as described (41). Cells were thought to both insert into highly curved membranes as wedges.…”

Section: Discussionmentioning

confidence: 99%

“…To avoid liposomal aggregates, 20 μg proteinase K was subsequently added, followed by another incubation at 45°C for 40 minutes. Small aliquots (1-2 μl) of vesicle suspension were freeze-fractured as described (41). Immunogold labeling at freeze-fracture replicas without proteinase K incubation was done using specific anti-REEP1 primary antibodies (1:50) followed by a gold-conjugated secondary antibody (1:50, 10 nm gold; British Biocell International).…”

Section: Methodsmentioning

confidence: 99%

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

Beetz¹,

Koch²,

Khundadze³

et al. 2013

J. Clin. Invest.

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Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature-inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival.

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“…Neurons in A1 were selected for recording if they displayed a pyramidal-shaped cell body, in agreement with the morphology of principal neurons in the mouse cortex. Interneurons, which are usually smaller and exhibit very high input resistance values, were avoided 50 . mEPSCs were recorded at a holding potential of −70 mV for at least 5 min in aCSF.…”

Section: Resultsmentioning

confidence: 99%

Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

Teichert¹,

Liebmann

Hübner

et al. 2017

Sci Rep

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It has been demonstrated that sensory deprivation results in homeostatic adjustments recovering neuronal activity of the deprived cortex. For example, deprived vision multiplicatively scales up mEPSC amplitudes in the primary visual cortex, commonly referred to as synaptic scaling. However, whether synaptic scaling also occurs in auditory cortex after auditory deprivation remains elusive. Using periodic intrinsic optical imaging in adult mice, we show that conductive hearing loss (CHL), initially led to a reduction of primary auditory cortex (A1) responsiveness to sounds. However, this was followed by a complete recovery of A1 activity evoked sounds above the threshold for bone conduction, 3 days after CHL. Over the same time course patch-clamp experiments in slices revealed that mEPSC amplitudes in A1 layers 2/3 pyramids scaled up multiplicatively in CHL mice. No recovery of sensory evoked A1 activation was evident in TNFα KO animals, which lack synaptic scaling. Additionally, we could show that the suppressive effect of sounds on visually evoked visual cortex activity completely recovered along with TNFα dependent A1 homeostasis in WT animals. This is the first demonstration of homeostatic multiplicative synaptic scaling in the adult A1. These findings suggest that mild hearing loss massively affects auditory processing in adult A1.Homeostatic plasticity is essential in maintaining a stable firing rate in neurons to compensate for prolonged perturbations of neuronal activity 1,2 . For example, a prolonged reduction of neuronal activity of cultured neocortical neurons generated compensatory changes returning firing levels back to control values 1 . Such homeostatic regulations are typically accompanied by an additional insertion of 2-amino-3-(3-hydroxy-5-methyl-isoxasol-4-yl) propanoic acid receptors (AMPARs) into all synapses of a neuron, leading to multiplicatively scaled up mEPSC (miniature excitatory postsynaptic currents) amplitudes or, "synaptic scaling" 2,3 . Specifically, this mechanism is described to globally increase (or decrease) the strength of each synapse of a neuron by the same factor in a multiplicative manner which allows the conservation of information stored in the synaptic weights 4 . Previous studies have demonstrated that synaptic scaling also takes place in vivo, e.g. after reduction of sensory cortex activity due to sensory deprivation. For example, visual deprivation by intraocular TTX injections, dark exposure, binocular enucleation or retinal lesions scales up AMPAR mediated mEPSC amplitudes in layers 2/3 pyramids of the primary visual cortex (V1) in juvenile and adult mice [5][6][7][8][9] . Furthermore, it was shown that prolonged visual deprivation increases visually evoked V1 responses during the visual critical period 10 . However, evidence for homeostatic synaptic scaling in primary auditory cortex and its effects on cortical responsiveness following auditory deprivation is rare.Previously, two models for induction of an auditory deprivation have been used, sensorineural hearing...

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Synaptic Glutamate Release Is Modulated by the Na⁺-Driven Cl⁻/HCO₃⁻Exchanger Slc4a8

Cited by 72 publications

References 66 publications

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

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