Lithium decreases Cl−–ATPase activity and increases intracellular Cl− concentration in cultured rat hippocampal neurons

Yagyu, Kyoko; Kitagawa, Kaori; Irie, Takao; Hattori, Naoki; Omori, Kyoko; Inagaki, Chiyoko

doi:10.1016/s0006-8993(99)01132-4

Cited by 13 publications

(3 citation statements)

References 14 publications

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“…Because of the lack of selective dyes for measuring intracellular Cl − , information on the basal level of intracellular [Cl − ] is limited and sometimes conflicting, ranging from 4.2 to 60 mM (Bomsztyk et al 1988;Inoue et al 1991;Hille 1992;Garcia et al 1997;Pilas and Durack 1997;Yagyu et al 1999); the extracellular [Cl − ] is likely to be around 120 mM (Hille 1992). Given the concentration gradient of Cl − across the membrane, opening Cl − channels should result in Cl − moving into the cell.…”

Section: Discussionmentioning

confidence: 99%

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

Wei

Xiao

Jin

et al. 2004

Pfl�gers Archiv European Journal of Physiology

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K+ and Cl- homeostasis have been implicated in cell volume regulation and apoptosis. We addressed the hypothesis that K+ and Cl- efflux may contribute to apoptotic cell shrinkage and apoptotic death in cultured cortical neurons. CLC-2 and CLC-3 chloride channels were detected in cultured cortical neurons. The Cl- channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) inhibited the outwardly rectifying Cl- current, prevented apoptotic cell shrinkage, and mildly attenuated cell death induced by staurosporine, C2-ceramide, or serum deprivation. Cl- channel blockers, however, at concentrations that prevented cell shrinkage had no significant effects on caspase activation and/or DNA fragmentation. Cell death in the presence of a Cl- channel blocker was still sensitive to blockade by the caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethyl ketone (z-VAD-fmk). Electron microscopy revealed that, although DIDS prevented apoptotic cell shrinkage, certain apoptotic ultrastructural alterations still took place in injured neurons. On the other hand, the K+ channel blocker tetraethylammonium (TEA), clofilium, or the caspase inhibitor z-VAD-fmk prevented cell shrinkage as well as caspase activation and/or DNA damage, and showed stronger neuroprotection against apoptotic alterations and cell death. The results indicate that neurons may undergo apoptotic process without cell shrinkage and imply distinct roles for Cl- and K+ homeostasis in regulating different apoptotic events.

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Section: Discussionmentioning

confidence: 99%

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

Wei

Xiao

Jin

et al. 2004

Pfl�gers Archiv European Journal of Physiology

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“…1994), regulation by phosphatidylinositol (PI) metabolism of in situ Cl − ‐ATPase activity has been suggested. Lithium, an inhibitor of inositol monophosphatase, was found to decrease Cl − ‐ATPase activity in cultured rat hippocampal neurons under the conditions of stimulated PI turnover (Yagyu et al . 1999).…”

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confidence: 99%

Amyloid β proteins inhibit Cl⁻‐ATPase activity in cultured rat hippocampal neurons

Yagyu

Kitagawa

Irie

et al. 2001

Journal of Neurochemistry

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Cl 2 -ATPase in the CNS is a candidate for an outwardly directed neuronal Cl 2 transporter requiring phosphatidylinositol-4-phosphate (PI4P) for its optimal activity. To test its pathophysiological changes in a phosphatidylinositol (PI) metabolism disorder, the effects of neurotoxic factors in Alzheimer's disease (AD), amyloid b proteins (Abs), on the Cl 2 -ATPase activity were examined using primary cultured rat hippocampal neurons. Amyloid b proteins (1±40, 1±42 and 25±35) concentration-dependently (1±100 nM) and timedependently (from 1 h to 6 day) decreased Cl 2 -ATPase activity and elevated intracellular Cl 2 concentrations ([Cl 2 ] i ), Ab25±35 being the most potent. Addition of inositol or 8-Brcyclic GMP completely reversed these Ab-induced changes. The recoveries in enzyme activity were attenuated by an inhibitor of PI 4-kinase, 10 mM wortmannin or 20 mM quercetin, but not by a PI 3-kinase inhibitor, 50 nM wortmannin or 10 mM LY294002. The PI, PIP and PIP2 levels of the plasma membrane-rich fraction were lower in the Ab-treated cells as compared with each control. In the Ab-exposed culture, but not in control, stimulation by 10 mM glutamate for 10 min signi®cantly increased fragmentation of DNA and decreased cell viability. Addition of inositol or 8-Br-cyclic GMP prevented the effect of Ab-treatment on the neurotoxicity of glutamate. Thus, Abs reduce neuronal Cl 2 -ATPase activity, resulting in an increase in [Cl 2 ] i probably by lowering PI4P levels, and this may re¯ect a pre-apoptotic condition in early pathophysiological pro®les of AD.

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“…BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Assay of ATPase activities. ATPase activities were determined by spectrophotometric measurement of inorganic phosphate liberated as described previously (16). The assay was carried out for 15 min at 37°C in 200 l of reaction buffer containing 100 mM Tris-Mes (pH 7.4), 1 mM EDTA-Tris, 100 mM NaCl, 10 mM KCl, 6 mM magnesium acetate, 6 mM ATP-Tris (pH 7.4, Sigma), 2 mM NaN 3 , and 14 -20 g of membrane protein with or without 1 mM ouabain and/or 0.3 mM ethacrynic acid.…”

Section: Fluorometric Measurement Of [Clmentioning

confidence: 99%

Molecular Cloning and Characterization of the Cl− Pump-Associated 55-kDa Protein in Rat Brain

Kitagawa

Yagyu

Yamamoto

et al. 2001

Biochemical and Biophysical Research Communications

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Lithium decreases Cl−–ATPase activity and increases intracellular Cl− concentration in cultured rat hippocampal neurons

Cited by 13 publications

References 14 publications

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

Amyloid β proteins inhibit Cl⁻‐ATPase activity in cultured rat hippocampal neurons

Molecular Cloning and Characterization of the Cl− Pump-Associated 55-kDa Protein in Rat Brain

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Lithium decreases Cl−–ATPase activity and increases intracellular Cl− concentration in cultured rat hippocampal neurons

Cited by 13 publications

References 14 publications

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

Effects of chloride and potassium channel blockers on apoptotic cell shrinkage and apoptosis in cortical neurons

Amyloid β proteins inhibit Cl−‐ATPase activity in cultured rat hippocampal neurons

Molecular Cloning and Characterization of the Cl− Pump-Associated 55-kDa Protein in Rat Brain

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Product

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Amyloid β proteins inhibit Cl⁻‐ATPase activity in cultured rat hippocampal neurons