- Poster presentation
- Open Access
Effects of a reduced efficacy of the KCC2 co-transporter in temporal lobe epilepsy: single neuron and network study
BMC Neuroscience volume 16, Article number: P5 (2015)
Epilepsy is one of the most common neurological disorders. Seizures in about 40% of patients with temporal lobe epilepsies are pharmaco-resistant . In surgically removed hippocampal tissue from these patients, the KCC2 cotransporter is absent or non-functional in about 20 % of subicular pyramidal cells . KCC2 normally assures the maintenance of low intra-neuronal chloride levels  and also regulates potassium levels . Chloride concentration changes in the remaining pyramidal cells due to intensive GABAergic input during seizures could reverse the effects of GABA currents from inhibitory to excitatory [5, 6]. Such changes may shift a pyramidal cell into a periodic bursting regime associated with ictal discharges. Using a detailed biophysical model of a single cell incorporating these mechanisms of ionic homeostasis and a neural network model, we show that decreasing the activity of KCC2 pump leads to repetitive seizure-like firing in the pathologic network due to increased extracellular potassium and intracellular chloride (Fig. 1). This model provides insights into how a dysregulation of pyramidal cell chloride homeostasis due to reduced levels of the KCC2 cotransporter may lead to seizures in the epileptic human subiculum.
Beghi E, Berg A, Carpio A, Forsgren L, Hesdorffer DC, Hauser WA, Tomson T: Comment on epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005, 46 (10): 1698-1699.
Huberfeld G, Wittner L, Clemenceau S, Baulac M, Kaila K, Miles R, Rivera C: Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. J Neuroscience. 2007, 27 (37): 9866-9873.
Blaesse P, Airaksinen MS, Rivera C, Kaila K: Cation-chloride cotransporters and neuronal function. Neuron. 2009, 61 (6): 820-838.
Payne JA: Functional characterization of the neuronal-specific K-Cl cotransporter: implications for [K+] oregulation. American Journal of Physiology-Cell Physiology. 1997, 273 (5): C1516-C1525.
Khalilov I, Dzhala V, Ben-Ari Y, Khazipov R: Dual role of GABA in the neonatal rat hippocampus. Developmental Neuroscience. 1999, 21 (3-5): 310-319.
Jedlicka P, Deller T, Gutkin BS, Backus KH: Activity-dependent intracellular chloride accumulation and diffusion controls GABA-A receptor-mediated synaptic transmission. Hippocampus. 2011, 21 (8): 885-898.
This work has been supported by the following grants: ANR-10-LABX-0087 IEC, ANR-10-IDEX-0001-02 PSL, ERC-322721, FRM FDT20140930942. Especially we would like to thank Giri Krishnan for useful discussions.
About this article
Cite this article
Buchin, A., Huberfeld, G., Miles, R. et al. Effects of a reduced efficacy of the KCC2 co-transporter in temporal lobe epilepsy: single neuron and network study. BMC Neurosci 16, P5 (2015). https://0-doi-org.brum.beds.ac.uk/10.1186/1471-2202-16-S1-P5
- Neural Network Model
- Pyramidal Cell
- Temporal Lobe Epilepsy
- Potassium Level
- Ionic Homeostasis