Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: CLC-3 channels modulate excitatory synaptic transmission in hippocampal neurons.

Authors: Xue Qing Wang, Ludmila V Deriy, Sarah Foss, Ping Huang, Fred S Lamb, Marcia A Kaetzel, Vytautas Bindokas, Jeremy D Marks, Deborah J Nelson

Journal, date & volume: Neuron, 2006 Oct 19 , 52, 321-33

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17046694

Abstract
It is well established that ligand-gated chloride flux across the plasma membrane modulates neuronal excitability. We find that a voltage-dependent Cl(-) conductance increases neuronal excitability in immature rodents as well, enhancing the time course of NMDA receptor-mediated miniature excitatory postsynaptic potentials (mEPSPs). This Cl(-) conductance is activated by CaMKII, is electrophysiologically identical to the CaMKII-activated CLC-3 conductance in nonneuronal cells, and is absent in clc-3(-/-) mice. Systematically decreasing [Cl(-)](i) to mimic postnatal [Cl(-)](i) regulation progressively decreases the amplitude and decay time constant of spontaneous mEPSPs. This Cl(-)-dependent change in synaptic strength is absent in clc-3(-/-) mice. Using surface biotinylation, immunohistochemistry, electron microscopy, and coimmunoprecipitation studies, we find that CLC-3 channels are localized on the plasma membrane, at postsynaptic sites, and in association with NMDA receptors. This is the first demonstration that a voltage-dependent chloride conductance modulates neuronal excitability. By increasing postsynaptic potentials in a Cl(-) dependent fashion, CLC-3 channels regulate neuronal excitability postsynaptically in immature neurons.