DOI: 10.1002/hipo.10014. Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

10.1002/hipo.10014

Crossref journal-article

Wiley

Hippocampus (311)

Abstract

AbstractFour genes encode electroneutral, Na+‐independent, K–Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl− to low concentrations and shift the reversal potential for Cl− conductances such as GABAA or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl− concentration in neurons decreases and γ‐aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal‐specific K–Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c‐fos, and the significant loss of parvalbumin‐positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABAA receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4–P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life. Hippocampus 2002;12:258–268. © 2002 Wiley‐Liss, Inc.

Bibliography

Woo, N., Lu, J., England, R., McClellan, R., Dufour, S., Mount, D. B., Deutch, A. Y., Lovinger, D. M., & Delpire, E. (2002). Hyperexcitability and epilepsy associated with disruption of the mouse neuronalâspecific KâCl cotransporter gene. Hippocampus, 12(2), 258â268. Portico.

Authors 9

Nam‐Sik Woo (first)
Jianming Lu (additional)
Roger England (additional)
Robert McClellan (additional)
Samuel Dufour (additional)
David B. Mount (additional)
Ariel Y. Deutch (additional)
David M. Lovinger (additional)
Eric Delpire (additional)

References 49 Referenced 253

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Dates

Type	When
Created	23 years ago (Aug. 25, 2002, 7:44 p.m.)
Deposited	1 year, 9 months ago (Nov. 19, 2023, 5:04 a.m.)
Indexed	1 week, 1 day ago (Aug. 19, 2025, 6:59 a.m.)
Issued	23 years, 7 months ago (Jan. 1, 2002)
Published	23 years, 7 months ago (Jan. 1, 2002)
Published Online	23 years, 6 months ago (Feb. 25, 2002)
Published Print	23 years, 7 months ago (Jan. 1, 2002)

Funders 0

None

BibTeX

@article{Woo_2002, title={Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene}, volume={12}, ISSN={1098-1063}, url={http://dx.doi.org/10.1002/hipo.10014}, DOI={10.1002/hipo.10014}, number={2}, journal={Hippocampus}, publisher={Wiley}, author={Woo, Nam‐Sik and Lu, Jianming and England, Roger and McClellan, Robert and Dufour, Samuel and Mount, David B. and Deutch, Ariel Y. and Lovinger, David M. and Delpire, Eric}, year={2002}, month=jan, pages={258–268} }

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      [
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        1
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  "alternative-id": [
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  "relation": {},
  "ISSN": [
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    "1098-1063"
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  "subject": [],
  "container-title-short": "Hippocampus",
  "published": {
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        2002,
        1
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}