Heteromultimers of DEG/ENaC Subunits Form H+-Gated Channels in Mouse Sensory Neurons

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 4; pp. 2338 - 2343
• Main Authors: Benson, Christopher J., Xie, Jinghie, Wemmie, John A., Price, Margaret P., Henss, Jillian M., Welsh, Michael J., Snyder, Peter M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.02.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Animals; Biological Sciences; Biology; Chemical composition; Cloning, Molecular; Complementary DNA; COS Cells; Degenerin Sodium Channels; DNA, Complementary - metabolism; Dose response relationship; Electrophysiology; Epithelial Sodium Channels; Ganglia, Spinal - metabolism; Hydrogen - metabolism; Hydrogen-Ion Concentration; Inurement; Ion Channels - chemistry; Ion Channels - physiology; Kinetics; Mice; Mice, Knockout; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - physiology; Neurology; Neurons; Neurons - metabolism; Neurons, Afferent - metabolism; Neuroscience; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Rodents; Sensory neurons; Sodium Channels - chemistry; Time Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.032678399

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.