Perturbed Chloride Homeostasis and GABAergic Signaling in Human Temporal Lobe Epilepsy
By G. Huberfeld, Lucia Wittner, S. Clemenceau, M. Baulac, Kai Kaila, R. Miles, C. Rivera. Journal of Neuroscience, 2007
605 citations recorded by the source corpus.
Changes in chloride (Cl−) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl− homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this human tissue generated a spontaneous interictal-like activity that was initiated in the subiculum. Records from a minority of subicular pyramidal cells revealed depolarizing GABAA receptor-mediated postsynaptic events, indicating a perturbed Cl− homeostasis. We assessed possible contributions of changes in expression of the potassium–chloride cotransporter KCC2. Double in situ hybridization showed that mRNA for KCC2 was absent from ∼30% of CaMKIIα (calcium/calmodulin-dependent protein kinase IIα)-positive subicular pyramidal cells. Combining intracellular recordings with biocytin-filled electrodes and KCC2 immunochemistry, we observed that all cells that were hyperpolarized during interictal events were immunopositive for KCC2, whereas the majority of depolarized cells were immunonegative. Bumetanide, at doses that selectively block the chloride-importing potassium–sodium–chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABAA reversal potentials and suppressed interictal activity. Changes in Cl− transporter expression thus contribute to human epileptiform activity, and molecules acting on these transporters may be useful antiepileptic drugs.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/f87741fb9865acbe1fd37c72c2dce7e32a1377be
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In Cellular and Molecular Neuroscience
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In Molecular Biology
In Psychiatry and Mental health
Citations in the corpus
- Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning (2015, background): “Bumetanide, at doses that selectively block the chloride-importing potassiumsodium-chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABAA reversal potentials and suppressed p-ripple activity (Huberfeld et al., 2007).”