title: Cloning and functional expression of a new epithelial sodium channel delta 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 alpha, beta and gamma subunits are abundantly expressed in epithelial tissues, where they have been well characterized. An ENaC delta subunit has also been described in the human nervous system, although its histological distribution pattern remains unexplored. We have now isolated a novel ENaC delta isoform (delta2) from human brain and studied the expression pattern of both the known (delta1) and the new (delta2) isoforms in the human and monkey telencephalon. ENaC delta2 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 beta and gamma accessory subunits. Comparison with the classical ENaC channel (alphabetagamma) indicates that the interaction between delta2, beta and gamma is functionally inefficient. Both ENaC delta 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.
authors.affiliation: Unidad de Farmacología, Universidad de La Laguna, La Laguna, Tenerife, Spain. giraldez@ull.es
authors.forename: Teresa
authors.initials: T
authors.lastname: Giraldez
authors.forename: Domingo
authors.initials: D
authors.lastname: Afonso-Oramas
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cruz-Muros
authors.forename: Victor
authors.initials: V
authors.lastname: Garcia-Marin
authors.forename: Philipp
authors.initials: P
authors.lastname: Pagel
authors.forename: Tomás
authors.initials: T
authors.lastname: González-Hernández
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarez de la Rosa
mesh_terms: D000818:Animals; D003001:Cloning, Molecular / Q000379:methods; D053503:Epithelial Sodium Channels / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D000882:Haplorhini; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008845:Microinjections / Q000379:methods; D008875:Middle Aged; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D020033:Protein Isoforms / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013687:Telencephalon / Q000166:cytology*; D014982:Xenopus laevis
chemical_list: D053503:Epithelial Sodium Channels; D020033:Protein Isoforms; D012333:RNA, Messenger