Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus.
Nat Neurosci
; 14(4): 487-94, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21378974
ABSTRACT
The absence of the chloride channel CLC-3 in Clcn3(-/-) mice results in hippocampal degeneration with a distinct temporal-spatial sequence that resembles neuronal loss in temporal lobe epilepsy. We examined how the loss of CLC-3 might affect GABAergic synaptic transmission in the hippocampus. An electrophysiological study of synaptic function in hippocampal slices taken from Clcn3(-/-) mice before the onset of neurodegeneration revealed a substantial decrease in the amplitude and frequency of miniature inhibitory postsynaptic currents compared with those in wild-type slices. We found that CLC-3 colocalized with the vesicular GABA transporter VGAT in the CA1 region of the hippocampus. Acidification of inhibitory synaptic vesicles induced by Cl(-) showed a marked dependence on CLC-3 expression. The decrease in inhibitory transmission in Clcn3(-/-) mice suggests that the neurotransmitter loading of synaptic vesicles was reduced, which we attribute to defective vesicular acidification. Our observations extend the role of Cl(-) in inhibitory transmission from that of a postsynaptic permeant species to a presynaptic regulatory element.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terminações Pré-Sinápticas
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Canais de Cloreto
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Transmissão Sináptica
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Ácido gama-Aminobutírico
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Hipocampo
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Inibição Neural
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article