A furosemide-sensitive K+-Cl−cotransporter counteracts intracellular Cl− accumulation and depletion in cultured rat midbrain neurons

• Verfasst von: Jarolimek, Wolfgang [VerfasserIn]
• Verfasst von: Lewen, Andrea [VerfasserIn]
• Verfasst von: Misgeld, Ulrich [VerfasserIn]
• Titel: A furosemide-sensitive K+-Cl−cotransporter counteracts intracellular Cl− accumulation and depletion in cultured rat midbrain neurons
• Verf.angabe: Wolfgang Jarolimek, Andrea Lewen, and Ulrich Misgeld
• E-Jahr: 1999
• Jahr: 15 June 1999
• Umfang: 10 S.
• Teil: volume:19
• Teil: year:1999
• Teil: number:12
• Teil: pages:4695-4704
• Teil: extent:10
• Fussnoten: Im Text sind "+" und "-" hochgestellt ; Gesehen am 27.04.2021
• Titel Quelle: Enthalten in: The journal of neuroscience
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 1999
• Band/Heft Quelle: 19(1999), 12, Seite 4695-4704
• ISSN Quelle: 1529-2401
• DOI: doi:10.1523/JNEUROSCI.19-12-04695.1999
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cl− depletion
• Sach-SW: Cl− homeostasis
• Sach-SW: Cl−accumulation
• Sach-SW: cultured neurons
• Sach-SW: Donnan equilibrium
• Sach-SW: furosemide
• Sach-SW: K+-Cl− cotransporter
• K10plus-PPN: 1756011079

Abstract

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.