| First Author | Rivera C | Year | 2004 |
| Journal | J Neurosci | Volume | 24 |
| Issue | 19 | Pages | 4683-91 |
| PubMed ID | 15140939 | Mgi Jnum | J:96890 |
| Mgi Id | MGI:3573823 | Doi | 10.1523/JNEUROSCI.5265-03.2004 |
| Citation | Rivera C, et al. (2004) Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J Neurosci 24(19):4683-91 |
| abstractText | GABA-mediated fast-hyperpolarizing inhibition depends on extrusion of chloride by the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained interictal-like activity in hippocampal slices downregulates KCC2 mRNA and protein expression in CA1 pyramidal neurons, which leads to a reduced capacity for neuronal Cl- extrusion. This effect is mediated by endogenous BDNF acting on tyrosine receptor kinase B (TrkB), with down-stream cascades involving both Shc/FRS-2 (src homology 2 domain containing transforming protein/FGF receptor substrate 2) and PLCgamma (phospholipase Cgamma)-cAMP response element-binding protein signaling. The plasmalemmal KCC2 has a very high rate of turnover, with a time frame that suggests a novel role for changes in KCC2 expression in diverse manifestations of neuronal plasticity. A downregulation of KCC2 may be a general early response involved in various kinds of neuronal trauma. |
