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

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• dc.contributor.author Lau, Davidca
• dc.contributor.author Vega-Saenz de Miera, Eleazarca
• dc.contributor.author Contreras, Diegoca
• dc.contributor.author Ozaita Mintegui, Andrés, 1969-ca
• dc.contributor.author Harvey, Michaelca
• dc.contributor.author Chow, Alanca
• dc.contributor.author Noebels, Jeffrey L.ca
• dc.contributor.author Paylor, Richardca
• dc.contributor.author Morgan, James I.ca
• dc.contributor.author Leonard, Christopher S.ca
• dc.contributor.author Rudy, Bernardoca
• dc.date.accessioned 2012-07-05T06:54:20Z
• dc.date.available 2012-07-05T06:54:20Z
• dc.date.issued 2000ca
• 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.format.mimetype application/pdfca
• dc.identifier.citation Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A et al. 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. DOI: 10.1523/jneurosci.20-24-09071.2000ca
• dc.identifier.doi http://dx.doi.org/10.1523/jneurosci.20-24-09071.2000
• dc.identifier.issn 0270-6474ca
• dc.identifier.uri http://hdl.handle.net/10230/16671
• dc.language.iso engca
• dc.publisher Society for Neuroscienceca
• dc.relation.ispartof Journal of Neuroscience. 2000;20(24):9071-85
• dc.rights © 2000, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/20/24/9071ca
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• 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 proteinsca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersion