Cloning and functional expression of a new epithelial sodium channel δ subunit isoform differentially expressed in neurons of the human and monkey telencephalon

Abstract

Epithelial sodium channel (ENaC) is a member of the ENaC/degenerin family of amiloride-sensitive, non-voltage gated sodium ion channels. ENaC α, β and γ subunits are abundantly expressed in epithelial tissues, where they have been well characterized. An ENaC δ subunit has also been described in the human nervous system, although its histological distribution pattern remains unexplored. We have now isolated a novel ENaC δ isoform (δ2) from human brain and studied the expression pattern of both the known (δ1) and the new (δ2) isoforms in the human and monkey telencephalon. ENaC δ2 is produced by a combination of alternative transcription start sites, a frame shift in exon 3 and alternative splicing of exon 4. It forms functional amiloride-sensitive sodium channels when co-expressed with ENaC β and γ accessory subunits. Comparison with the classical ENaC channel (αβγ) indicates that the interaction between δ2, β and γ is functionally inefficient. Both ENaC δ isoforms are widely expressed in pyramidal cells of the human and monkey cerebral cortex and in different neuronal populations of telencephalic subcortical nuclei, but double-labelling experiments demonstrated a low level of co-localization between isoforms (5-8%), suggesting specific functional roles for each of them. © 2007 The Authors.