| First Author | Wang XQ | Year | 2006 |
| Journal | Neuron | Volume | 52 |
| Issue | 2 | Pages | 321-33 |
| PubMed ID | 17046694 | Mgi Jnum | J:122982 |
| Mgi Id | MGI:3716051 | Doi | 10.1016/j.neuron.2006.08.035 |
| Citation | Wang XQ, et al. (2006) CLC-3 channels modulate excitatory synaptic transmission in hippocampal neurons. Neuron 52(2):321-33 |
| abstractText | 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. |
