期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 22, 页码 8465-8468出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0602979103
关键词
chloride transporter; GABA(A) receptors; Xenopus oocytes
The mRNA levels of NKCC1, an inwardly directed Na+, K+-2Cl(-) cotransporter that facilitates the accumulation of intracellular Cl-, and of KCC2, an outwardly directed K+-Cl- cotransporter that extrudes Cl-, were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses of the mRNAs extracted from the human TLE-associated brain regions revealed an up-regulation of NKCC1 mRNA and a down-regulation of KCC2 mRNA in the hippocampal subiculum, compared with the hippocampus proper or the TL neocortex, suggesting an abnormal transcription of Cl- transporters in the TLE subiculum. In parallel experiments, cell membranes isolated from the same TLE-associated brain regions were injected into Xenopus oocytes that rapidly incorporated human GABA(A) receptors into their surface membrane. The GABA currents elicited in oocytes injected with membranes from the subiculum had a more depolarized reversal potential (E-GABA) compared with the hippocampus proper or the neocortex. The NKCC1 blocker bumetanicle or a temperature decrease of 10 degrees C shifted the GABA-current EGABA more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the EGABA of TL neocortex-injected oocytes. We conclude that the anomalous expression of both Cl- transporters, KCC1 and NKCC2, in TLE hippocampal subiculum probably causes altered Cl- transport in the epileptic neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly exciting, a feature that may contribute to the precipitation of epileptic seizures.
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