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.

Keywords: CIRK; GIRK; ataxia; hyperpolarization; maturation.