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PMID:21378974

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Citation

Riazanski, V, Deriy, LV, Shevchenko, PD, Le, B, Gomez, EA and Nelson, DJ (2011) Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus. Nat. Neurosci. 14:487-94

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.

Links

PubMed PMC3072292 Online version:10.1038/nn.2775

Keywords

Animals; CA1 Region, Hippocampal/metabolism; CA1 Region, Hippocampal/ultrastructure; Chloride Channels/deficiency; Chloride Channels/genetics; Chloride Channels/physiology; Hippocampus/metabolism; Hippocampus/ultrastructure; Hydrogen-Ion Concentration; Inhibitory Postsynaptic Potentials/genetics; Mice; Mice, Knockout; Neural Inhibition/genetics; Neural Inhibition/physiology; Organ Culture Techniques; Presynaptic Terminals/metabolism; Presynaptic Terminals/ultrastructure; Rats; Rats, Wistar; Synaptic Transmission/genetics; Synaptic Vesicles/metabolism; Synaptic Vesicles/ultrastructure; Vesicular Inhibitory Amino Acid Transport Proteins/physiology; gamma-Aminobutyric Acid/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:VIAAT

located_in

GO:0060077: inhibitory synapse

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:O35458

C

Seeded From UniProt

complete

MOUSE:VIAAT

located_in

GO:0008021: synaptic vesicle

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:O35458

C

Seeded From UniProt

complete

MOUSE:CLCN3

located_in

GO:0060077: inhibitory synapse

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P51792

C

Seeded From UniProt

complete

MOUSE:CLCN3

located_in

GO:0008021: synaptic vesicle

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P51792

C

Seeded From UniProt

complete

MOUSE:CLCN3

acts_upstream_of_or_within

GO:0051932: synaptic transmission, GABAergic

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447864

P

Seeded From UniProt

complete

MOUSE:CLCN3

acts_upstream_of_or_within

GO:0097401: synaptic vesicle lumen acidification

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447864

P

Seeded From UniProt

complete

MOUSE:VGLU1

located_in

GO:0008021: synaptic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:VGLU1

part_of

GO:0008021: synaptic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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