Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

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Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, Noebels JL, Paylor R, Morgan JI, Leonard CS, Rudy B. Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci. 2000; 20(24): 9071-85
http://hdl.handle.net/10230/16671
To cite or link this document: http://hdl.handle.net/10230/16671
dc.contributor.author Lau, David
dc.contributor.author Vega-Saenz de Miera, Eleazar
dc.contributor.author Contreras, Diego
dc.contributor.author Ozaita Mintegui, Andrés
dc.contributor.author Harvey, Michael
dc.contributor.author Chow, Alan
dc.contributor.author Noebels, Jeffrey L.
dc.contributor.author Paylor, Richard
dc.contributor.author Morgan, James I.
dc.contributor.author Leonard, Christopher S.
dc.contributor.author Rudy, Bernardo
dc.date.accessioned 2012-07-05T06:54:20Z
dc.date.available 2012-07-05T06:54:20Z
dc.date.issued 2000
dc.identifier.citation Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, Noebels JL, Paylor R, Morgan JI, Leonard CS, Rudy B. Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci. 2000; 20(24): 9071-85
dc.identifier.issn 0270-6474
dc.identifier.uri http://hdl.handle.net/10230/16671
dc.description.abstract Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 −/− mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.
dc.language.iso eng
dc.publisher Society for Neuroscience
dc.relation.ispartof J Neurosci. 2000; 20(24): 9071-85
dc.rights (c) 2000, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/20/24/9071
dc.subject.other Xarxes neuronals (Neurobiologia)
dc.subject.other Neurones -- Fisiologia
dc.title Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins
dc.type info:eu-repo/semantics/article
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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