Astrocytes from mouse brain slices express ClC-2-mediated Cl− currents regulated during development and after injury

Makara, Judit K.; Rappert, Angelika; Matthias, Katja; Steinhäuser, Christian; Spät, András; Kettenmann, Helmut

doi:10.1016/s1044-7431(03)00080-0

Cited by 47 publications

(42 citation statements)

References 52 publications

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“…Light microscopy cannot resolve whether ClC-2 is expressed on the membrane of oligodendrocytic or astrocytic membrane at such contact sites. Because ClC-2 was detected (albeit not enriched) in myelin preparations and because subtypes of astrocytes are known to express ClC-2 (Ferroni et al, 1997;Sik et al, 2000;Makara et al, 2003) (Fig. 4 A), either localization is plausible.…”

Section: Discussionmentioning

confidence: 92%

Leukoencephalopathy upon Disruption of the Chloride Channel ClC-2

Blanz¹,

Schweizer²,

Auberson³

et al. 2007

Journal of Neuroscience

153

204

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ClC-2 is a broadly expressed plasma membrane chloride channel that is modulated by voltage, cell swelling, and pH. A human mutation leading to a heterozygous loss of ClC-2 has previously been reported to be associated with epilepsy, whereas the disruption of Clcn2 in mice led to testicular and retinal degeneration. We now show that the white matter of the brain and spinal cord of ClC-2 knock-out mice developed widespread vacuolation that progressed with age. Fluid-filled spaces appeared between myelin sheaths of the central but not the peripheral nervous system. Neuronal morphology, in contrast, seemed normal. Except for the previously reported blindness, neurological deficits were mild and included a decreased conduction velocity in neurons of the central auditory pathway. The heterozygous loss of ClC-2 had no detectable functional or morphological consequences. Neither heterozygous nor homozygous ClC-2 knock-out mice had lowered seizure thresholds. Sequencing of a large collection of human DNA and electrophysiological analysis showed that several ClC-2 sequence abnormalities previously found in patients with epilepsy most likely represent innocuous polymorphisms.

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Section: Discussionmentioning

confidence: 92%

Leukoencephalopathy upon Disruption of the Chloride Channel ClC-2

Blanz¹,

Schweizer²,

Auberson³

et al. 2007

Journal of Neuroscience

153

204

View full text Add to dashboard Cite

show abstract

“…ClC-2 is a widely expressed plasma membrane Cl À channel that slowly activates on hyperpolarization, cell swelling and moderately acidic extracellular pH 13,15 . These characteristics were observed in heterologous overexpression and in native cells 9,28 including neurons 29,30 and astrocytes [31][32][33] . Upon heterologous co-expression, GlialCAM increases ClC-2 currents and drastically changes their properties from inwardly rectifying to a nearly ohmic current-voltage relationship, an effect that does not require GlialCAM-GlialCAM trans-interactions 12 .…”

Section: Clcn2mentioning

confidence: 83%

Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction

et al. 2014

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“…Indeed, Clchannels can be regulated by a number of intracellular and extracellular signals, including protein kinase A (PKA) (Berger et al, 1991;Tewari et al, 2000), PKC (Berger et al, 1993;Kawasaki et al, 1994;Uchida et al, 1994), pH (Kajita and Brown, 1997;Sauve et al, 2000;Tewari et al, 2000;Diewald et al, 2002), and Ca 2+ (Sauve et al, 2000;Stewart et al, 2001). Moreover, several studies have demonstrated that the differentiation and/or proliferation stage of a cell can alter the expression and/or the activity of Cl -channels Rutledge et al, 2001;Furukawa et al, 2002;Zheng et al, 2002;Makara et al, 2003). Therefore, it appears likely that different Cl -channels will function under different biological conditions.…”

Section: Chloride Channel Gene Candidates Expressed In Cortical Astromentioning

confidence: 99%

Biophysical and pharmacological characterization of hypotonically activated chloride currents in cortical astrocytes

Parkerson

Sontheimer

2004

Glia

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Rat cortical astrocytes regulate their cell volume in response to hypotonic challenge. This regulation is believed to depend largely on the release of chloride or organic osmolytes through anion channels. Using whole-cell recordings, we identified weakly outwardly rectifying chloride currents that could be activated in response to hypotonic challenge. These currents exhibited the following permeability sequence upon replacement of chloride in the bathing solution with various anions: I ->NO 3 ->Cl ->Gluc -≥MeS ->Ise -. Interestingly, extracellular I -, albeit showing the greatest permeability, blocked the currents with an IC 50 of ≈50 mM. Currents were almost completely inhibited by 123 μM NPPB and partially inhibited by 200 μM niflumic acid or 200 μM DIDS. Additionally, the total number of Cl -ions effluxed through the hypotonically activated channels was markedly similar to the total solute efflux during volume regulation. We therefore propose the hypotonically activated chloride channel as a major contributor to volume regulation of astrocytes. To examine potential candidate chloride channel genes expressed by astrocytes, we employed RTPCR to demonstrate the presence of transcripts for ClC-2, 3, 4, 5, and 7, as well as for VDAC and CFTR in cultured astrocytes. Moreover, we performed immunostaining with antibodies against each of these channels and showed the strongest expression of ClC-2 and ClC-3, strong expression of ClC-5 and VDAC, weak expression of ClC-7 and very weak expression of ClC-4 and CFTR. Intriguingly, although we found at least seven Cl -channel proteins from three different gene families in astrocytes, none appeared to be active in resting cells.

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Astrocytes from mouse brain slices express ClC-2-mediated Cl− currents regulated during development and after injury

Cited by 47 publications

References 52 publications

Leukoencephalopathy upon Disruption of the Chloride Channel ClC-2

Leukoencephalopathy upon Disruption of the Chloride Channel ClC-2

Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction

Biophysical and pharmacological characterization of hypotonically activated chloride currents in cortical astrocytes

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