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Titolo:
Hippocampal heterotopia lack functional kv4.2 potassium channels in the methylazoxymethanol model of cortical malformations and epilepsy
Autore:
Castro, PA; Cooper, EC; Lowenstein, DH; Baraban, SC;
Indirizzi:
Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston,MA 02115 USA Harvard Univ Boston MA USA 02115 ed Ctr, Dept Neurol, Boston,MA 02115 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 17, volume: 21, anno: 2001,
pagine: 6626 - 6634
SICI:
0270-6474(20010901)21:17<6626:HHLFKP>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURONAL MIGRATION DISORDERS; INTRACTABLE PARTIAL EPILEPSY; K+ CHANNEL; PYRAMIDAL NEURONS; ELECTROPHYSIOLOGICAL PROPERTIES; SEIZURE SUSCEPTIBILITY; PRENATAL TREATMENT; DYSPLASTIC CORTEX; PATCH-CLAMP; FETAL RATS;
Keywords:
epilepsy; dysplasia; heterotopia; hippocampus; patch-clamp; potassium channel;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Baraban, SC Univ Calif San Francisco, Dept Neurol Surg, Box 0520,513 Parnassus Ave, San Francisco, CA 94143 USA Univ Calif San Francisco Box 0520,513Parnassus Ave San Francisco CA USA 94143
Citazione:
P.A. Castro et al., "Hippocampal heterotopia lack functional kv4.2 potassium channels in the methylazoxymethanol model of cortical malformations and epilepsy", J NEUROSC, 21(17), 2001, pp. 6626-6634

Abstract

Human cortical malformations often result in severe forms of epilepsy. Although the morphological properties of cells within these malformations are well characterized, very little is known about the function of these cells. In rats, prenatal methylazoxymethanol (MAM) exposure produces distinct nodules of disorganized pyramidal-like neurons (e.g., nodular heterotopia) andloss of lamination in cortical and hippocampal structures. Hippocampal nodular heterotopias are prone to hyperexcitability and may contribute to the increased seizure susceptibility observed in these animals. Here we demonstrate that heterotopic pyramidal neurons in the hippocampus fail to express a potassium channel subunit corresponding to the fast, transient A-type current. In situ hybridization and immunohistochemical analysis revealed markedly reduced expression of Kv4.2 (A-type) channel subunits in heterotopic cell regions of the hippocampus of MAM-exposed rats. Patch-clamp recordings from visualized heterotopic neurons indicated a lack of fast, transient (I-A)-type potassium current and hyperexcitable firing. A-type currents were observed on normotopic pyramidal neurons in MAM-exposed rats and on interneurons, CA1 pyramidal neurons, and cortical layer V-VI pyramidal neurons in saline-treated control rats. Changes in A-current were not associated with analteration in the function or expression of delayed, rectifier (Kv2.1) potassium channels on heterotopic cells. We conclude that heterotopic neurons lack functional A-type Kv4.2 potassium channels and that this abnormality could contribute to the increased excitability and decreased seizure thresholds associated with brain malformations in MAM-exposed rats.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 10:06:33