Reverse NCX Attenuates Cellular Sodium Loading in Metabolically Compromised Cortex

Gerkau, Niklas J.; Rakers, Cordula; Durry, Simone; Petzold, Gabor C.; Rose, Christine R.

doi:10.1093/cercor/bhx280

Cited by 52 publications

(134 citation statements)

References 105 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…In addition, we performed SDS-PAGE and Western blots of tissue dissected from corpus callosum of animals at different postnatal stages (P5, 10,15,25). For both GLT-1 and GLAST several distinct bands (60,130, 180 kd and 55, 130, 150, 190 kd, respectively) were detected in all age groups most likely due to monomeric and multimeric fractions of the transporters ( Figure 7A), confirming earlier studies indicating that both exist as homomultimers [45,46].…”

Section: Spatial and Developmental Expression Profile Of Glutamate-assupporting

confidence: 85%

“…Moreover, sodium influx into astrocytes changes the driving force for sodium-dependent secondary active transporters. For example, this may result in the reversal of the plasma membrane Na + /Ca 2+ -exchanger (NCX), which then switches from a calcium exporter to an importer for calcium, contributing to intracellular calcium increases under both physiological and pathophysiological conditions [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Action Potential Firing Induces Sodium Transients in Macroglial Cells of the Mouse Corpus Callosum

et al. 2018

View full text Add to dashboard Cite

Recent work has established that glutamatergic synaptic activity induces transient sodium elevations in grey matter astrocytes by stimulating glutamate transporter 1 (GLT-1) and glutamate-aspartate transporter (GLAST). Glial sodium transients have diverse functional consequences but are largely unexplored in white matter. Here, we employed ratiometric imaging to analyse sodium signalling in macroglial cells of mouse corpus callosum. Electrical stimulation resulted in robust sodium transients in astrocytes, oligodendrocytes and NG2 glia, which were blocked by tetrodotoxin, demonstrating their dependence on axonal action potentials (APs). Action potential-induced sodium increases were strongly reduced by combined inhibition of ionotropic glutamate receptors and glutamate transporters, indicating that they are related to release of glutamate. While AMPA receptors were involved in sodium influx into all cell types, oligodendrocytes and NG2 glia showed an additional contribution of NMDA receptors. The transporter subtypes GLT-1 and GLAST were detected at the protein level and contributed to glutamate-induced glial sodium signals, indicating that both are functionally relevant for glutamate clearance in corpus callosum. In summary, our results demonstrate that white matter macroglial cells experience sodium influx through ionotropic glutamate receptors and glutamate uptake upon AP generation. Activity-induced glial sodium signalling may thus contribute to the communication between active axons and macroglial cells.

show abstract

Section: Spatial and Developmental Expression Profile Of Glutamate-assupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Action Potential Firing Induces Sodium Transients in Macroglial Cells of the Mouse Corpus Callosum

et al. 2018

View full text Add to dashboard Cite

show abstract

“…; Gerkau et al . ). Briefly, SBFI‐AM‐loaded organotypic tissue slices were first superfused with nominally Na + ‐free calibration‐ACSF, containing ouabain (100 µ m ), an inhibitor of the Na + /K + ‐ATPase, as well as the ionophores gramicidin (3 µ m ) and monensin (10 µ m ) to equilibrate intra‐ and extracellular Na + .…”

Section: Methodsmentioning

confidence: 97%

“…; Gerkau et al . ), increasing [Na + ] caused a decrease in fluorescence emission of SBFI and traces were inverted for illustration purposes after normalization to fluorescence levels at 0 m m (Fig. A ).…”

Section: Methodsmentioning

confidence: 99%

“…Afterwards, slices were exposed to calibration-ACSFs containing different [Na + ] and resulting changes in SBFI fluorescence in neuronal somata were recorded using multiphoton excitation. As reported before (Rose et al 1999;Meier et al 2006;Gerkau et al 2018), increasing [Na + ] caused a decrease in fluorescence emission of SBFI and traces were inverted for illustration purposes after normalization to fluorescence levels at 0 mM ( Fig. 1A).…”

Section: Sodium Imagingmentioning

confidence: 99%

See 1 more Smart Citation

Relation between activity‐induced intracellular sodium transients and ATP dynamics in mouse hippocampal neurons

Gerkau

Lerchundi

Nelson

et al. 2019

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Employing quantitative Na+‐imaging and Förster resonance energy transfer‐based imaging with ATeam1.03YEMK (ATeam), we studied the relation between activity‐induced Na+ influx and intracellular ATP in CA1 pyramidal neurons of the mouse hippocampus. Calibration of ATeam in situ enabled a quantitative estimate of changes in intracellular ATP concentrations. Different paradigms of stimulation that induced global Na+ influx into the entire neuron resulted in decreases in [ATP] in the range of 0.1–0.6 mm in somata and dendrites, while Na+ influx that was locally restricted to parts of dendrites did not evoke a detectable change in dendritic [ATP]. Our data suggest that global Na+ transients require global cellular activation of the Na+/K+‐ATPase resulting in a consumption of ATP that transiently overrides its production. For recovery from locally restricted Na+ influx, ATP production as well as fast intracellular diffusion of ATP and Na+ might prevent a local drop in [ATP]. Abstract Excitatory neuronal activity results in the influx of Na+ through voltage‐ and ligand‐gated channels. Recovery from accompanying increases in intracellular Na+ concentrations ([Na+]i) is mainly mediated by the Na+/K+‐ATPase (NKA) and is one of the major energy‐consuming processes in the brain. Here, we analysed the relation between different patterns of activity‐induced [Na+]i signalling and ATP in mouse hippocampal CA1 pyramidal neurons by Na+ imaging with sodium‐binding benzofurane isophthalate (SBFI) and employing the genetically encoded nanosensor ATeam1.03YEMK (ATeam). In situ calibrations demonstrated a sigmoidal dependence of the ATeam Förster resonance energy transfer ratio on the intracellular ATP concentration ([ATP]i) with an apparent KD of 2.6 mm, indicating its suitability for [ATP]i measurement. Induction of recurrent network activity resulted in global [Na+]i oscillations with amplitudes of ∼10 mm, encompassing somata and dendrites. These were accompanied by a steady decline in [ATP]i by 0.3–0.4 mm in both compartments. Global [Na+]i transients, induced by afferent fibre stimulation or bath application of glutamate, caused delayed, transient decreases in [ATP]i as well. Brief focal glutamate application that evoked transient local Na+ influx into a dendrite, however, did not result in a measurable reduction in [ATP]i. Our results suggest that ATP consumption by the NKA following global [Na+]i transients temporarily overrides its availability, causing a decrease in [ATP]i. Locally restricted Na+ transients, however, do not result in detectable changes in local [ATP]i, suggesting that ATP production, together with rapid intracellular diffusion of both ATP and Na+ from and to unstimulated neighbouring regions, counteracts a local energy shortage under these conditions.

show abstract

Roles of glial ion transporters in brain diseases

Song

Luo

Sun

et al. 2019

Glia

View full text Add to dashboard Cite

Glial ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions of the central nervous system (CNS). In response to acute or chronic brain injuries, these ion transporters can be activated and differentially regulate glial functions, which has subsequent impact on brain injury or tissue repair and functional recovery. In this review, we summarized the current knowledge about major glial ion transporters, including Na+/H+ exchangers (NHE), Na+/Ca2+ exchangers (NCX), Na+–K+–Cl− cotransporters (NKCC), and Na+–HCO3− cotransporters (NBC). In acute neurological diseases, such as ischemic stroke and traumatic brain injury (TBI), these ion transporters are rapidly activated and play significant roles in regulation of the intra‐ and extracellular pH, Na+, K+, and Ca2+ homeostasis, synaptic plasticity, and myelin formation. However, overstimulation of these ion transporters can contribute to glial apoptosis, demyelination, inflammation, and excitotoxicity. In chronic brain diseases, such as glioma, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), glial ion transporters are involved in the glioma Warburg effect, glial activation, neuroinflammation, and neuronal damages. These findings suggest that glial ion transporters are involved in tissue structural and functional restoration, or brain injury and neurological disease development and progression. A better understanding of these ion transporters in acute and chronic neurological diseases will provide insights for their potential as therapeutic targets.

show abstract

Reverse NCX Attenuates Cellular Sodium Loading in Metabolically Compromised Cortex

Cited by 52 publications

References 105 publications

Action Potential Firing Induces Sodium Transients in Macroglial Cells of the Mouse Corpus Callosum

Action Potential Firing Induces Sodium Transients in Macroglial Cells of the Mouse Corpus Callosum

Relation between activity‐induced intracellular sodium transients and ATP dynamics in mouse hippocampal neurons

Roles of glial ion transporters in brain diseases

Contact Info

Product

Resources

About