Tetraethylammonium Block of the BNC1 Channel

• Published in: Biophysical journal 1999-03, Vol.76 (3), p.1377-1383
• Main Authors: Adams, Christopher M., Price, Margaret P., Snyder, Peter M., Welsh, Michael J.
• Format: Article
• Language: English
• Subjects: Acid Sensing Ion Channels; Animals; Binding Sites - genetics; Biophysical Phenomena; Biophysics; Brain; Cells; Degenerin Sodium Channels; Epithelial Sodium Channels; Humans; In Vitro Techniques; Ion Channels; Membrane Potentials; Membranes; Models, Biological; Mutagenesis, Site-Directed; Mutation; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Oocytes - metabolism; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Sodium Channel Blockers; Sodium Channels - chemistry; Sodium Channels - genetics; Tetraethylammonium - pharmacology; Xenopus laevis
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(99)77299-1

The brain Na + channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430) that lies N-terminal to the second membrane-spanning domain activates BNC1 and converts it from a Na +-selective channel to one permeable to both Na + and K +. Because all K + channels are blocked by tetraethylammonium (TEA), we asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply voltage-dependent and was reduced when current was outward, suggesting multi-ion block within the channel pore. Block was dependent on the size of the quaternary ammonium; the smaller tetramethylammonium blocked with similar properties, whereas the larger tetrapropylammonium had little effect. When residue 430 was Phe, the effects of tetramethylammonium and tetrapropylammonium were not altered. In contrast, block by TEA was much less voltage-dependent, suggesting that the Phe mutation introduced a new TEA binding site located ∼30% of the way across the electric field. These results provide insight into the structure and function of BNC1 and suggest that TEA may be a useful tool to probe function of this channel family.