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The Journal of Neuroscience, June 15, 1999, 19(12):4695-4704
A Furosemide-Sensitive K+-Cl
Cotransporter Counteracts Intracellular Cl Accumulation
and Depletion in Cultured Rat Midbrain Neurons
Wolfgang
Jarolimek,
Andrea
Lewen, and
Ulrich
Misgeld
I. Physiologisches Institut der Universität Heidelberg,
D-69120 Heidelberg, Germany
Efficacy of postsynaptic inhibition through GABAA
receptors 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 other
in vitro preparations of the mammalian brain. Tightseal whole-cell recording of spontaneous GABAA
receptor-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+]o
the 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.
Key words:
Cl homeostasis; K+-Cl cotransporter; furosemide; Cl depletion; Cl
accumulation; Donnan equilibrium; cultured neurons
Copyright © 1999 Society for Neuroscience 0270-6474/99/19124695-10$05.00/0
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