The regulation of pH in the central nervous system

Schlue, Wolf-Rüdiger; Dörner, R.

doi:10.1139/y92-273

Cited by 13 publications

(4 citation statements)

References 33 publications

(19 reference statements)

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“…Changes in extracellular pH may alter intracellular pH (Schlue & Dorner, 1992; Deitmer & Rose, 1996). To determine whether changes in intracellular pH are involved in the proton‐induced modulation of the csNSC currents, we have studied the effect of quinine, an agent known to cause intracellular alkalinization (Dixon et al .…”

Section: Resultsmentioning

confidence: 99%

Acidosis decreases low Ca²⁺ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Chu

Zhu

Wei

et al. 2003

The Journal of Physiology

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The effects of extracellular pH (pHo) on calcium‐sensing non‐selective cation (csNSC) channels in cultured mouse hippocampal neurons were investigated using whole‐cell voltage‐clamp and current‐clamp recordings. Decreasing extracellular Ca2+ concentrations ([Ca2+]o) activated slow and sustained inward currents through the csNSC channels. Decreasing pHo activated amiloride‐sensitive transient proton‐gated currents which decayed to baseline in several seconds. With proton‐gated channels inactivated by pre‐perfusion with low pH solution or blocked by amiloride, decreasing pHo to 6.5 inhibited the csNSC currents with a leftward shift of the Ca2+ dose–inhibition curve. Increasing pH to 8.5, on the other hand, caused a rightward shift of the Ca2+ dose–inhibition curve and potentiated the csNSC currents. Intracellular alkalinization following bath perfusion of quinine mimicked the potentiation of the csNSC currents by increasing pHo, while intracellular acidification by addition and subsequent withdrawal of NH4Cl mimicked the inhibition of the csNSC currents by decreasing pHo. Intracellular pH (pHi) imaging demonstrated that decreasing pHo induced a corresponding decrease in pHi. Including 30 mM Hepes in the pipette solution eliminated the effects of quinine and NH4Cl on the csNSC currents, but only partially reduced the effect of lowering pHo. In current‐clamp recordings, decreasing [Ca2+]o induced sustained membrane depolarization and excitation of hippocampal neurons. Decreasing pHo to 6.5 inhibited the low [Ca2+]o‐induced csNSC channel‐mediated membrane depolarization and the excitation of neurons. Our results indicate that acidosis may inhibit low [Ca2+]o‐induced neuronal excitation by inhibiting the activity of the csNSC channels. Both the extracellular and the intracellular sites are involved in the proton modulation of the csNSC channels.

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Section: Resultsmentioning

confidence: 99%

Acidosis decreases low Ca²⁺ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Chu

Zhu

Wei

et al. 2003

The Journal of Physiology

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“…Whether, in the normal presence of extracellular CO 2 and HCO 3 − , a Cl − extrusion is accomplished also by a Na + ‐dependent Cl–HCO 3 [(Na–HCO 3 )–(H–Cl)] exchanger ( Moody 1981, Moser 1985, Schlue & Dörner 1992) is as yet unclear. It might be surmised, though, that as primary pH adjuster a Na + ‐dependent Cl–HCO 3 exchanger would not carry Cl − in bulk quantities.…”

Section: Discussionmentioning

confidence: 99%

Cl^– transport in the lobster stretch receptor neurone

Theander

Edman

Fåhraeus

et al. 1999

Acta Physiologica Scandinavica

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Experiments were performed to identify mechanisms underlying non-leakage and non-H+/HCO3--linked transmembrane Cl- transports in the slowly adapting stretch receptor neurone of the European lobster, using intracellular microelectrode and pharmacological techniques. In methodological tests, it was established that direct estimates of intracellular Cl- with ion-sensitive microelectrodes are statistically identical with indirect estimates by means of a GABA method, where 1-2 mM GABA is transforming the cell's membrane voltage into its Cl- equilibrium voltage from which the Cl- concentration is inferred by the Nernst equation. From experiments using sodium orthovanadate and ethacrynic acid, supposed to block primary Cl- pumps, and bumetanide, supposed to block Na-K-Cl co-transporters, it appeared that neither of the two Cl- transport systems exists in the stretch receptor neurone. It could be shown, however, that the cell is equipped with an electroneutral K-Cl co-transporter that (a) is blockable by furosemide in high (Km approximately 350 microM), by 4-acetamido-4'-isothiocyanato-stilbene-2,2-disulphonic acid (SITS) in medium-high (Km approximately 35 microM), and by 4, 4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) in low (Km approximately 15 microM) doses, (b) is (transiently) activatable by (1 mM) n-ethylmaleimide, (c) is not suppressed by extracellular Rb+ or NH4+, and (d) is not directly coupled to any transmembrane transports of Na+, H+ or HCO3-. From functional tests, with varying transmembrane K+ and Cl- gradients, evidence obtained that the K-Cl co-transporter is able to reverse its transport direction and to adjust its transport rate in a considerable range. As a whole, the results speak in favour of the K-Cl co-transporter being responsible (a) for normally keeping the intracellular Cl- concentration at low levels, for an optimization of the cell's inhibitory system, and (b) for achieving fast transmembrane shifts of K+ (and Cl-), as a means of stabilizing the cell's membrane excitability in conditions of varying extracellular K+ concentrations.

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“…Included, because integral to the topic, are a brief overview of pH regulation in mammalian astrocytes and a consideration of the mechanisms by which K ϩ , glutamate, and ammonium induce pH changes. Several reviews offer the reader a broader perspective on the effects of pH on cell metabolism (Busa and Nuccitelli, 1984) and excitable membranes (Moody, 1984), and on the regulation and modulation of pH in the brain (Chesler, 1990;Chesler and Kaila, 1992;Schlue and Dörner, 1992) and specifically in glia (Deitmer and Rose, 1996).…”

Section: Introductionmentioning

confidence: 99%

Intracellular pH as a regulatory signal in astrocyte metabolism

Brookes

1997

Glia

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An intracellular alkalinization is observed in mammalian astrocytes in response to repetitive neuronal activity in vivo. The alkalinizing effect of potassium released from electrically active neurons predominates over many other influences on the intracellular pH of astrocytes, including acid loads induced by glutamate and ammonium. There is evidence that this pH signal, elicited by neuronal activity, may facilitate glucose utilization and glutamine formation in astrocytes. This short review surveys the mechanisms of the intracellular pH changes induced in astrocytes by extracellular potassium, glutamate, and ammonium. It then focuses upon the regulatory effects of these pH changes on glucose utilization, as estimated primarily by rates of deoxyglucose phosphorylation, and on the uptake and metabolism of glutamate. Many studies in this field exploit the advantages of astrocyte cell culture. However, the conditions of cell culture can diminish expression of the intracellular alkalinization induced by potassium and thus lead to underestimation of the metabolic significance of this pH signal. GLIA 21:64–73, 1997. © 1997 Wiley‐Liss, Inc.

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The regulation of pH in the central nervous system

Cited by 13 publications

References 33 publications

Acidosis decreases low Ca²⁺ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Acidosis decreases low Ca²⁺ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Cl^– transport in the lobster stretch receptor neurone

Intracellular pH as a regulatory signal in astrocyte metabolism

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The regulation of pH in the central nervous system

Cited by 13 publications

References 33 publications

Acidosis decreases low Ca2+ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Acidosis decreases low Ca2+ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Cl– transport in the lobster stretch receptor neurone

Intracellular pH as a regulatory signal in astrocyte metabolism

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Acidosis decreases low Ca²⁺ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Acidosis decreases low Ca²⁺ ‐induced neuronal excitation by inhibiting the activity of calcium‐sensing cation channels in cultured mouse hippocampal neurons

Cl^– transport in the lobster stretch receptor neurone