A furosemide-sensitive K+-Cl−cotransporter counteracts intracellular Cl− accumulation and depletion in cultured rat midbrain neurons
Efficacy of postsynaptic inhibition through GABAAreceptors in the mammalian brain depends on the maintenance of a Cl− gradient for hyperpolarizing Cl− currents. We have taken advantage of the reduced complexity under which Cl− regulation can be investigated in cultured neurons as opposed to neurons...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
15 June 1999
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| In: |
The journal of neuroscience
Year: 1999, Jahrgang: 19, Heft: 12, Pages: 4695-4704 |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.19-12-04695.1999 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1523/JNEUROSCI.19-12-04695.1999 Verlag, lizenzpflichtig, Volltext: https://www.jneurosci.org/content/19/12/4695 
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| Verfasserangaben: | Wolfgang Jarolimek, Andrea Lewen, and Ulrich Misgeld |
| Zusammenfassung: | Efficacy of postsynaptic inhibition through GABAAreceptors in the mammalian brain depends on the maintenance of a Cl− gradient for hyperpolarizing Cl− currents. We have taken advantage of the reduced complexity under which Cl− regulation can be investigated in cultured neurons as opposed to neurons in otherin vitro preparations of the mammalian brain. Tightseal whole-cell recording of spontaneous GABAAreceptor-mediated postsynaptic currents suggested that an outward Cl− transport reduced dendritic [Cl−]i if the somata of cells were loaded with Cl− via the patch pipette. We determined dendritic and somatic reversal potentials of Cl− currents induced by focally applied GABA to calculate [Cl−]i during variation of [K+]o and [Cl−] in the patch pipette. [Cl−]i and [K+]o were tightly coupled by a furosemide-sensitive K+-Cl−cotransport. Thermodynamic considerations excluded the significant contribution of a Na+-K+-Cl−cotransporter to the net Cl− transport. We conclude that under conditions of normal [K+]othe K+-Cl− cotransporter helps to maintain [Cl−]i at low levels, whereas under pathological conditions, under which [K+]o remains elevated because of neuronal hyperactivity, the cotransporter accumulates Cl− in neurons, thereby further enhancing neuronal excitability. |
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| Beschreibung: | Im Text sind "+" und "-" hochgestellt Gesehen am 27.04.2021 |
| Beschreibung: | Online Resource |
| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.19-12-04695.1999 |