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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to understand the effects of sodium channels on synaptic signaling and response in the cerebellum, it is essential to know for each class of neuron what sodium channel isoforms are present, and the properties and distribution of each. Sodium channels are heteromultimeric membrane proteins, consisting of a large alpha subunit that forms the pore, and one or more beta subunits. Ten genes encode an alpha subunit in mammals, and of these, four are expressed in the cerebellum: Nav1.1, Nav1.2, Nav1.3 and Nav1.6. Three genes encode beta subunits (Nabeta1-3), and all three are expressed in the cerebellum. However, Nav1.3 and Nabeta3 have been found only in the developing cerebellum. All sodium channels recorded in the cerebellum are TTX-sensitive with similar kinetics, making it difficult to identify the isoforms electrically. Thus, most of the expression studies have relied on techniques that allow visualization of sodium channel subtypes at the level of mRNA and protein. In situ hybridization and immunolocalization studies demonstrated that granule cells predominantly express Nav1.2, Nav1.6, Nabeta1, and Nabeta2. Protein for Nav1.2 and Nav1.6 is localized primarily in granule cell parallel fibers. Purkinje cells express Nav1.1, Nav1.6, Nabeta1 and Nabeta2. The somato-dendritic localization of Nav1.1 and Nav1.6 in Purkinje cells suggests that these isoforms are involved in the integration of synaptic input. Deep cerebellar nuclei neurons expressed Nav1.1 and Nav1.6 as well as Nabeta1. Bergmann glia expressed Nav1.6, but not granule cell layer astrocytes. Some sodium channel isoforms that are not expressed normally in the adult cerebellum are expressed in animals with mutations or disease. Electrophysiological studies suggest that Nav1.6 is responsible for spontaneous firing and bursting features in Purkinje cells, but the specialized functions of the other subunits in the cerebellum remain unknown.
Cerebellum 2003
PMID:Expression and distribution of voltage-gated sodium channels in the cerebellum. 1288 29

Voltage-gated sodium channels are responsible for action potential initiation and propagation in electrically excitable cells. In this study, we used biochemical, immunohistochemical and quantitative immunoelectron microscopy techniques to reveal the temporal and spatial expression of the Na(v)1.2 channel subunit in granule cells of cerebellum. Using histoblot, we detected Na(v)1.2 widely distributed in the adult brain, but prominently expressed in the cerebellum. During postnatal development, Na(v)1.2 mRNA and protein were detected low during the first and second postnatal week, increased to P15 and then continue to decrease until adult levels. At the light microscopic level, Na(v)1.2 immunoreactivity concentrated in the molecular layer of the cerebellar cortex. Using immunofluorescence, Na(v)1.2 colocalised with VGluT1, but not with VGluT2, demonstrating that the subunit was preferentially present in parallel fibre axons and axon terminals. At the electron microscopic level, Na(v)1.2 immunoparticles were exclusively detected at presynaptic sites in granule cell axons and axon terminals of granule cells, with occasional clustering in their axon initial segment. This was demonstrated using quantitative immunogold analysis. In the axon terminals, the distribution of Na(v)1.2 was relatively uniform along the extrasynaptic plasma membrane and never detected in the active zone. We could not find detectable levels of Na(v)1.2 at postsynaptic elements of granule cells or other cerebellar cell types. The present findings show a polarised distribution of Na(v)1.2 along the neuronal surface of granule cells and suggest its primary involvement in the transmission of information from granule cells to Purkinje cells.
Cerebellum 2013 Feb
PMID:Polarised localisation of the voltage-gated sodium channel Na(v)1.2 in cerebellar granule cells. 2252 69