Chloride Homeostasis in Neurons With Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels

Rahmati, Negah; Hoebeek, Freek E.; Peter, Saša; Zeeuw, Chris I. De

doi:10.3389/fncel.2018.00101

Cited by 47 publications

(50 citation statements)

References 315 publications

(316 reference statements)

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“…It pumps Cl − across the plasma membrane out of the cell. In contrast, NKCC1, which is widely expressed in central and peripheral neurons as well as glial cells, is encoded by SLC12a2 and facilitates uptake of Cl − into cells (13,28). KCC2 is composed of two splice variants: KCC2a and KCC2b.…”

Section: Physiological Effects Of Cation-chloride Cotransporters In Tmentioning

confidence: 99%

“…Based on experimental studies involving seizure models and epilepsy patients, we know that the down-regulation of GABA receptor subunits, loss of GABAergic interneurons, and decreased frequency and amplitude of spontaneous synaptic GABA currents from pyramidal neurons contribute to decreased GABAergic inhibition (7,(10)(11)(12). In neurons, NKCC1 and KCC2 serve as two main regulators of GABA receptors' function by maintaining [Cl − ] i homeostasis (13). A disruption in the balance between NKCC1 and KCC2 induced by unknown causes may result in ineffective GABA inhibition (14,15).…”

Section: Introductionmentioning

confidence: 99%

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Role of NKCC1 and KCC2 in Epilepsy: From Expression to Function

et al. 2020

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As a main inhibitory neurotransmitter in the central nervous system, γ-aminobutyric acid (GABA) activates chloride-permeable GABAa receptors (GABAa Rs) and induces chloride ion (Cl −) flow, which relies on the intracellular chloride concentration ([Cl − ] i) of the postsynaptic neuron. The Na-K-2Cl cotransporter isoform 1 (NKCC1) and the K-Cl cotransporter isoform 2 (KCC2) are two main cation-chloride cotransporters (CCCs) that have been implicated in human epilepsy. NKCC1 and KCC2 reset [Cl − ] i by accumulating and extruding Cl − , respectively. Previous studies have shown that the profile of NKCC1 and KCC2 in neonatal neurons may reappear in mature neurons under some pathophysiological conditions, such as epilepsy. Although increasing studies focusing on the expression of NKCC1 and KCC2 have suggested that impaired chloride plasticity may be closely related to epilepsy, additional neuroelectrophysiological research aimed at studying the functions of NKCC1 and KCC2 are needed to understand the exact mechanism by which they induce epileptogenesis. In this review, we aim to briefly summarize the current researches surrounding the expression and function of NKCC1 and KCC2 in epileptogenesis and its implications on the treatment of epilepsy. We will also explore the potential for NKCC1 and KCC2 to be therapeutic targets for the development of novel antiepileptic drugs.

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Section: Physiological Effects Of Cation-chloride Cotransporters In Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of NKCC1 and KCC2 in Epilepsy: From Expression to Function

et al. 2020

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“…Rahmati et al . (2017) discussed a list of putative candidates for Cl − uptake (e.g., AE2, AE3 and other members of the solute carrier family like Slc26A7 and SlcA11) 51 . Publicly available expression data in the Allen Mouse Brain Atlas indicates expression of several of these candidates in the NRT 52 .…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of chloride homeostasis and GABAergic transmission in the thalamus

Schmidt

Ghaffarian

Philippot

et al. 2018

Sci Rep

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The thalamus is important for sensory integration with the ventrobasal thalamus (VB) as relay controlled by GABAergic projections from the nucleus reticularis thalami (NRT). Depending on the [Cl−]i primarily set by cation-chloride-cotransporters, GABA is inhibitory or excitatory. There is evidence that VB and NRT differ in terms of GABA action, with classical hyperpolarization in VB due to the expression of the Cl− extruder KCC2 and depolarizing/excitatory GABA action in the NRT, where KCC2 expression is low and Cl− accumulation by the Cl− inward transporter NKCC1 has been postulated. However, data on NKCC1 expression and functional analysis of both transporters are missing. We show that KCC2-mediated Cl− extrusion set the [Cl−]i in VB, while NKCC1 did not contribute substantially to Cl− accumulation and depolarizing GABA action in the NRT. The finding that NKCC1 did not play a major role in NRT neurons is of high relevance for ongoing studies on the therapeutic use of NKCC1 inhibitors trying to compensate for a disease-induced up-regulation of NKCC1 that has been described for various brain regions and disease states like epilepsy and chronic pain. These data suggest that NKCC1 inhibitors might have no major effect on healthy NRT neurons due to limited NKCC1 function.

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“…Intra-neuronal ion stricture is a significant factor that predetermines brain functioning. There is evidence that abnormal homeostasis of CL-([CL-] i) cellular concentration together with Na+ и Ca2+ induces disorders in neurons excitability and nerve transmission thus making for occurrence of neurologic pathologies [30][31][32][33].…”

Section: __________________________ T a B L E 2 Mental Performance Ofmentioning

confidence: 99%

Irrational lighting as a health risk occurring in the Arctic

Kaptsov¹

2020

Health Risk Analysis

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We assessed health risks for operators who had to live in mobile houses in the Arctic regions. Inadequate lighting is a most significant factor related to housing conditions that can cause various pathologies resulting in decreasing working capacity. We revised data on impacts exerted by luminous and LED lighting on operators and it allowed us to determine reasons for "aftereffects" produced by LED lighting regarding an increase in latency in No. 95 pattern electroretinogram (PERG); this latency characterizes a situation with ganglionic cells in the visual analyzer. We put forward a hypothesis that lower "inhibition" efficiency was caused by absorption of blue light within 380-450 nanometers range, and an increase in PERG P50 amplitude was caused by an additional increase in Na + , Ca + ions flows when ChR2 protein absorbed excessive 470 nm blue light against a blue light dose in a luminous lamp spectrum. We showed that there were practically no changes in operators' health after they had been exposed to dynamic LED lighting; however, all the participants in the experiment had a W-like splitting in P100 peak in visually induced cortical potentials as a response to stimuli with different angle sizes. When ganglionic cells are exposed to blue lighting, interaction between their degrading mitochondria and astrocytes becomes very important. LED lighting results in damage to mitochondria in ganglionic cells. Mitochondria are moved to the optic nerve head to be utilized where they are absorbed by astrocytes and eliminated with their lysosome. Should a speed of degrading mitochondria inflow exceed a speed at which they are utilized, it will cause mechanic strains in fibers of the optic nerve head due to "mitochondria jam"; this, in its turn, can lead to long-term disorders in the optic nerve head and glaucoma occurrence. We formulated recommendations for the State Standard 23274-84 "Mobile houses. Electrical appliances. Overall technical conditions" and advised applying semiconductor white light sources in them as they had a biologically adequate irradiation spectrum.

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Chloride Homeostasis in Neurons With Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels

Cited by 47 publications

References 315 publications

Role of NKCC1 and KCC2 in Epilepsy: From Expression to Function

Role of NKCC1 and KCC2 in Epilepsy: From Expression to Function

Differential regulation of chloride homeostasis and GABAergic transmission in the thalamus

Irrational lighting as a health risk occurring in the Arctic

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