Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells
dc.contributor.author | Osorio, Nancy | en_US |
dc.contributor.author | Cathala, Laurence | en_US |
dc.contributor.author | Meisler, Miriam H. | en_US |
dc.contributor.author | Crest, Marcel | en_US |
dc.contributor.author | Magistretti, Jacopo | en_US |
dc.contributor.author | Delmas, Patrick | en_US |
dc.date.accessioned | 2011-01-13T19:53:45Z | |
dc.date.available | 2011-01-13T19:53:45Z | |
dc.date.issued | 2010-02-15 | en_US |
dc.identifier.citation | Osorio, Nancy; Cathala, Laurence; Meisler, Miriam H.; Crest, Marcel; Magistretti, Jacopo; Delmas, Patrick; (2010). "Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells." The Journal of Physiology 588(4): 651-670. <http://hdl.handle.net/2027.42/78706> | en_US |
dc.identifier.issn | 0022-3751 | en_US |
dc.identifier.issn | 1469-7793 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/78706 | |
dc.description.abstract | Cerebellar granule (CG) cells generate high-frequency action potentials that have been proposed to depend on the unique properties of their voltage-gated ion channels. To address the in vivo function of Nav1.6 channels in developing and mature CG cells, we combined the study of the developmental expression of Nav subunits with recording of acute cerebellar slices from young and adult granule-specific Scn8a KO mice. Nav1.2 accumulated rapidly at early-formed axon initial segments (AISs). In contrast, Nav1.6 was absent at early postnatal stages but accumulated at AISs of CG cells from P21 to P40. By P40–P65, both Nav1.6 and Nav1.2 co-localized at CG cell AISs. By comparing Na + currents in mature CG cells (P66–P74) from wild-type and CG-specific Scn8a KO mice, we found that transient and resurgent Na + currents were not modified in the absence of Nav1.6 whereas persistent Na + current was strongly reduced. Action potentials in conditional Scn8a KO CG cells showed no alteration in threshold and overshoot, but had a faster repolarization phase and larger post-spike hyperpolarization. In addition, although Scn8a KO CG cells kept their ability to fire action potentials at very high frequency, they displayed increased interspike-interval variability and firing irregularity in response to sustained depolarization. We conclude that Nav1.6 channels at axon initial segments contribute to persistent Na + current and ensure a high degree of temporal precision in repetitive firing of CG cells. | en_US |
dc.format.extent | 1403125 bytes | |
dc.format.extent | 3106 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.title | Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Physiology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Human Genetics, 4909 Buhl, University of Michigan, Ann Arbor, MI 48109-0618, USA | en_US |
dc.contributor.affiliationother | Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 6231, CNRS, Université de la Méditerranée, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France | en_US |
dc.contributor.affiliationother | Physiologie cérébrale, Université Paris Descartes, CNRS UMR 8118, 45 Rue des Saints Pères, 75006 Paris, France | en_US |
dc.contributor.affiliationother | Dipartimento di Fisiologia, Università degli Studi di Pavia, Via Forlanini 6, 27100 Pavia, Italy | en_US |
dc.identifier.pmid | 20173079 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/78706/1/jphysiol.2010.183798.pdf | |
dc.identifier.doi | 10.1113/jphysiol.2010.183798 | en_US |
dc.identifier.source | The Journal of Physiology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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