title: Distinct expression patterns of inwardly rectifying potassium currents in developing cerebellar granule cells of the hemispheres and the vermis.
abstract: G-protein-coupled inwardly rectifying potassium (GIRK) channels play a crucial role during the migration and maturation of cerebellar granule cells (GCs) in the vermis. In the cerebellar hemispheres, however, only minor effects on the development of GCs are observed in mice with GIRK channel impairment. This regional difference may reflect distinct ontogenetic expression patterns of GIRK channels. Therefore, inwardly rectifying responses in mice were characterized at different stages of development in the vermis and the hemispheres. In the vermis, GCs in the premigratory zone (PMZ) at P7-P15 exhibit GIRK current but not constitutive inwardly rectifying potassium (CIRK) current, and are relatively depolarized at rest. In contrast, premigratory GCs in the hemispheres express only CIRK channels, which accounts for their more hyperpolarized resting membrane potential. Furthermore, the pattern of voltage-dependent inward currents in the PMZ GCs of cerebellar hemispheres is consistent with a more mature stage of development than the corresponding GCs in the vermis, resulting in robust firing properties mediated by sodium channels. Later in development (P21-P22), CIRK current is then observed in the majority of vermis GCs. This developmental pattern, revealed by electrophysiological recordings, was confirmed by immunohistological experiments that showed greater reactivity for GIRK2 in the PMZ of the vermis than in the hemispheres during development (P7-P15). These findings suggest that regional differences in development are responsible for the differential expression of inwardly rectifying potassium channels in the vermis and in the hemispheres.
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy.|Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Brandalise
authors.affiliation: Instituto de Investigación en Discapacidades Neurológicas (IDINE), Department of Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, Albacete, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lujan
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: Roberta
authors.initials: R
authors.lastname: Leone
authors.affiliation: Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lodola
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cesaroni
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Romano
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Gerber
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rossi
mesh_terms: D000818:Animals; D065814:Cerebellar Vermis / Q000378:metabolism / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497069:Kcnj6 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying
keywords: CIRK; GIRK; ataxia; hyperpolarization; maturation