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J Physiol Volume 569, Number 3, 801-816, December 15, 2005 DOI: 10.1113/jphysiol.2005.097022
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Differential targeting and functional specialization of sodium channels in cultured cerebellar granule cells

Nancy Osorio1, Gisèle Alcaraz2, Françoise Padilla1, François Couraud2, Patrick Delmas1 and Marcel Crest1

1 Neurophysiologie Cellulaire, CNRS, UMR 6150
2 Neurobiologie des Canaux Ioniques, INSERM, U641, IFR Jean Roche, Faculté de Médecine, Boulevard Pierre Dramard, 13916, Marseille Cedex 20, France

The ion channel dynamics that underlie the complex firing patterns of cerebellar granule (CG) cells are still largely unknown. Here, we have characterized the subcellular localization and functional properties of Na+ channels that regulate the excitability of CG cells in culture. As evidenced by RT-PCR and immunocytochemical analysis, morphologically differentiated CG cells expressed Nav1.2 and Nav1.6, though both subunits appeared to be differentially regulated. Nav1.2 was localized at most axon initial segments (AIS) of CG cells from 8 days in vitro DIV 8 to DIV 15. At DIV 8, Nav1.6 was found uniformly throughout somata, dendrites and axons with occasional clustering in a subset of AIS. Accumulation of Nav1.6 at most AIS was evident by DIV 13–14, suggesting it is developmentally regulated at AIS. The specific contribution of these differentially distributed Na+ channels has been assessed using a combination of methods that allowed discrimination between functionally compartmentalized Na+ currents. In agreement with immunolocalization, we found that fast activating–fully inactivating Na+ currents predominate at the AIS membrane and in the somatic plasma membrane.

(Received 19 August 2005; accepted after revision 5 October 2005; first published online 6 October 2005)
Corresponding author P. Delmas: Laboratoire de Neurophysiologie Cellulaire, CNRS UMR 6150, IFR Jean Roche, Faculté de Médecine, Boulevard Pierre Dramard, 13916, Marseille Cedex 20, France. Email: delmas.p{at}jean-roche.univ-mrs.fr




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J. Magistretti, L. Castelli, L. Forti, and E. D'Angelo
Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study
J. Physiol., May 15, 2006; 573(1): 83 - 106.
[Abstract] [Full Text] [PDF]




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