title: Electrostatic charge at position 552 affects the activation and permeation of FMRFamide-gated Na+ channels.
abstract: The FMRFamide-gated Na(+) channel (FaNaC) is a unique peptide-gated sodium channel and a member of the epithelial sodium channel/degenerin family. Previous studies have shown that an aspartate residue (Asp(552)) in the second transmembrane domain is involved in activation of the FaNaC. To examine the significance of a negative charge at position 552, we used a cysteine-modification method. Macroscopic currents of a cysteine mutant (D552C) were potentiated or inhibited by use of positively or negatively charged sulfhydryl reagents ([2-(trimethylammonium)ethyl]methanethiosulfonate bromide, MTSET, and sodium (2-sulfonatoethyl)methanethiosulfonate, MTSES, respectively). Dose-response analysis showed that treatment with MTSET increased the potency of the FMRFamide in the FaNaC whereas treatment with MTSES reduced the maximum response. Negative charge at position 552 was necessary for the characteristic inward rectification of the FaNaC. These results suggest that negative electric charge at position 552 is important to the activation and permeation properties of the FaNaC.
authors.affiliation: Laboratory of Neurobiology, Faculty of Integrated Arts and Sciences, Hiroshima University, Kagamiyama 1-7-1, Higashi-Hiroshima, 739-8521, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kodani
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001048:Aplysia / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000494:pharmacology*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008698:Mesylates / Q000494:pharmacology; D008958:Models, Molecular; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009865:Oocytes; D010539:Permeability; D011487:Protein Conformation; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013499:Surface Properties; D014982:Xenopus laevis
chemical_list: D008698:Mesylates; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; C109153:(2-sulfonatoethyl)methanethiosulfonate; C109154:(2-(trimethylammonium)ethyl)methanethiosulfonate; D019835:FMRFamide; D012964:Sodium; D003545:Cysteine