| First Author | Zhu L | Year | 2005 |
| Journal | J Neurophysiol | Volume | 93 |
| Issue | 3 | Pages | 1557-68 |
| PubMed ID | 15469961 | Mgi Jnum | J:110014 |
| Mgi Id | MGI:3630232 | Doi | 10.1152/jn.00616.2004 |
| Citation | Zhu L, et al. (2005) Cortical neurons lacking KCC2 expression show impaired regulation of intracellular chloride. J Neurophysiol 93(3):1557-68 |
| abstractText | As excitable cells, neurons experience constant changes in their membrane potential due to ion flux through plasma membrane channels. They maintain their transmembrane cation concentrations through robust Na(+)/K(+)-ATPase pump activity. During synaptic transmission and spread of action potentials, the concentration of the major anion, Cl-, is also under constant challenge from membrane potential changes. Moreover, intracellular Cl- is also affected by ligand-gated Cl- channels such as GABA(A) and glycine receptors. To regulate intracellular Cl- in an electrically silent manner, neurons couple the movement of Cl- with K+. In this study, we have used gene-targeted KCC2-/- mice to provide strong evidence that KCC2, the neuronal-specific K-Cl co-transporter, drives neuronal Cl- to low concentrations, shifting the GABA reversal potential toward more negative potentials, thus promoting hyperpolarizing GABA responses. Cortical neurons lacking KCC2, not only fail to show a developmental decrease in [Cl-]i, but also are unable to regulate [Cl-]i on Cl- loading or maintain [Cl]i during membrane depolarization. These data are consistent with the central role of KCC2 in promoting inhibition and preventing hyperexcitability. |
