Saxitoxin-sensitive Na+ channels: presynaptic localization in cerebellum and hippocampus of neurological mutant mice

The autoradiographic distribution of saxitoxin (STX) binding sites associated with voltage-sensitive Na+ channel was studied in the cerebellum of neurological weaver (wv/wv), Purkinje cell degeneration (pcd/pcd), nervous (nr/nr) and reeler (rl/rl) mutant mice. The Purkinje cell layer contains the highest density of STX binding sites in normal mice. High densities were observed in the molecular layer. Intermediate and very low densities were present in the granular layer and the white matter respectively. There was an important decrease of grain density in the molecular layer and Purkinje cell layer of wv/wv cerebellum, where a large majority of granular cells had disappeared. In pcd/pcd and nr/nr mutants, a small decrease was observed in Purkinje cell layer where the Purkinje cells had almost all degenerated. In rl/rl mutants where all neuronal cells were malpositioned, the compacted molecular layer contained an increased STX binding sites density. Conversely the labelling of Purkinje cells areas was decreased. The hippocampal formation of rl/rl mutants presents an homogeneous repartition of the Na+ channel protein in contrast with the laminated distribution observed in normal mice. Our autoradiographic data suggest that a major proportion of STX-sensitive Na+ channels are localized in parallel fibers of granular cells and in axons of basket cells in a presynaptic position. In Purkinje cells, the dendritic arborization seems to be devoid of STX binding sites conversely to somata.