Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus.

Authors: Vladimir Riazanski, Ludmila V Deriy, Pavel D Shevchenko, Brandy Le, Erwin A Gomez, Deborah J Nelson

Journal, date & volume: Nat. Neurosci., 2011 Apr , 14, 487-94

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/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.