Neuron type- and input pathway-dependent expression of Slc4a10 in adult mouse brains

Abstract

Slc4a10 was originally identified as a Na(+) -driven Cl(-) /HCO3 (-) exchanger NCBE that transports extracellular Na(+) and HCO3 (-) in exchange for intracellular Cl(-) , whereas other studies argue against a Cl(-) -dependence for Na(+) -HCO3 (-) transport, and thus named it the electroneutral Na(+) /HCO3 (-) cotransporter NBCn2. Here we investigated Slc4a10 expression in adult mouse brains by in situ hybridization and immunohistochemistry. Slc4a10 mRNA was widely expressed, with higher levels in pyramidal cells in the hippocampus and cerebral cortex, parvalbumin-positive interneurons in the hippocampus, and Purkinje cells (PCs) in the cerebellum. Immunohistochemistry revealed an uneven distribution of Slc4a10 within the somatodendritic compartment of cerebellar neurons. In the cerebellar molecular layer, stellate cells and their innervation targets (i.e. PC dendrites in the superficial molecular layer) showed significantly higher labeling than basket cells and their targets (PC dendrites in the basal molecular layer and PC somata). Moreover, the distal dendritic trees of PCs (i.e. parallel fiber-targeted dendrites) had significantly greater labeling than the proximal dendrites (climbing fiber-targeted dendrites). These observations suggest that Slc4a10 expression is regulated in neuron type- and input pathway-dependent manners. Because such an elaborate regulation is also found for K(+) -Cl(-) cotransporter KCC2, a major neuronal Cl(-) extruder, we compared their expression. Slc4a10 and KCC2 overlapped in most somatodendritic elements. However, relative abundance was largely complementary in the cerebellar cortex, with particular enrichments of Slc4a10 in PC dendrites and KCC2 in molecular layer interneurons, granule cells and PC somata. These properties might reflect functional redundancy and distinction of these transporters, and their differential requirements by individual neurons and respective input domains.

Keywords: NCBE; NCBn2; Slc4a10; bicarbonate exchanger; brain; mouse.