title: Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons.
abstract: Acidic extracellular solution activates transient H(+)-gated currents in dorsal root ganglion (DRG) neurons. The biophysical properties of three degenerin/epithelial sodium (DEG/ENaC) channel subunits (BNC1, ASIC, and DRASIC), and their expression in DRG, suggest that they might underlie these H(+)-gated currents and function as sensory transducers. However, it is uncertain which of these DEG/ENaC subunits generate the currents, and whether they function as homomultimers or heteromultimers. We found that the biophysical properties of transient H(+)-gated currents from medium to large mouse DRG neurons differed from BNC1, ASIC, or DRASIC expressed individually, but were reproduced by coexpression of the subunits together. To test the contribution of each subunit, we studied DRG from three strains of mice, each bearing a targeted disruption of BNC1, ASIC, or DRASIC. Deletion of any one subunit did not abolish H(+)-gated currents, but altered currents in a manner consistent with heteromultimerization of the two remaining subunits. These data indicate that combinations of two or more DEG/ENaC subunits coassemble as heteromultimers to generate transient H(+)-gated currents in mouse DRG neurons.
authors.affiliation: Department of Internal Medicine and Psychiatry, and Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA. chris-benson@uiowa.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Benson
authors.forename: Jinghui
authors.initials: J
authors.lastname: Xie
authors.forename: John A
authors.initials: JA
authors.lastname: Wemmie
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Price
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Henss
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: Peter M
authors.initials: PM
authors.lastname: Snyder
mesh_terms: D000818:Animals; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D062626:Degenerin Sodium Channels; D004594:Electrophysiology; D053503:Epithelial Sodium Channels; D005727:Ganglia, Spinal / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000737:chemistry*; D013997:Time Factors
chemical_list: D018076:DNA, Complementary; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D006859:Hydrogen