| First Author | Farmer LM | Year | 2013 |
| Journal | J Physiol | Volume | 591 |
| Issue | 4 | Pages | 1001-15 |
| PubMed ID | 23165767 | Mgi Jnum | J:205976 |
| Mgi Id | MGI:5547488 | Doi | 10.1113/jphysiol.2012.243485 |
| Citation | Farmer LM, et al. (2013) CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses. J Physiol 591(Pt 4):1001-15 |
| abstractText | The chloride channel CLC-3 is expressed in the brain on synaptic vesicles and postsynaptic membranes. Although CLC-3 is broadly expressed throughout the brain, the CLC-3 knockout mouse shows complete, selective postnatal neurodegeneration of the hippocampus, suggesting a crucial role for the channel in maintaining normal brain function. CLC-3 channels are functionally linked to NMDA receptors in the hippocampus; NMDA receptor-dependent Ca(2+) entry, activation of Ca(2+)/calmodulin kinase II and subsequent gating of CLC-3 link the channels via a Ca(2+)-mediated feedback loop. We demonstrate that loss of CLC-3 at mature synapses increases long-term potentiation from 135 +/- 4% in the wild-type slice preparation to 154 +/- 7% above baseline (P < 0.001) in the knockout; therefore, the contribution of CLC-3 is to reduce synaptic potentiation by approximately 40%. Using a decoy peptide representing the Ca(2+)/calmodulin kinase II phosphorylation site on CLC-3, we show that phosphorylation of CLC-3 is required for its regulatory function in long-term potentiation. CLC-3 is also expressed on synaptic vesicles; however, our data suggest functionally separable pre- and postsynaptic roles. Thus, CLC-3 confers Cl(-) sensitivity to excitatory synapses, controls the magnitude of long-term potentiation and may provide a protective limit on Ca(2+) influx. |
