title: Carboxyl methylation activates purified renal amiloride-sensitive Na+ channels in planar lipid bilayers.
abstract: The early increase in luminal membrane Na+ permeability by aldosterone in Na(+)-reabsorbing epithelia is attributed to an increase in the open probability (and number) of preexisting amiloride-sensitive Na+ channels. Carboxyl methylation reactions are involved, but the mechanism of action is unknown. We report that the 90-95-kDa polypeptide subunit of a purified renal Na+ channel protein can be specifically carboxymethylated and that this biochemical reaction, in the presence of guanosine 5'-3-O-(thio)triphosphate, leads directly to an increase in channel activity. Further, we show that protein kinase A-mediated phosphorylation can synergistically activate these channels. We suggest that renal Na+ channels have multiple biochemical regulatory inputs and that post-translational modifications underlie the increases in luminal membrane Na+ channel activity produced by aldosterone and vasopressin in Na(+)-reabsorbing epithelia.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham 35294.
authors.forename: I I
authors.initials: II
authors.lastname: Ismailov
authors.forename: J H
authors.initials: JH
authors.lastname: McDuffie
authors.forename: S
authors.initials: S
authors.lastname: Sariban-Sohraby
authors.forename: J P
authors.initials: JP
authors.lastname: Johnson
authors.forename: D J
authors.initials: DJ
authors.lastname: Benos
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D002417:Cattle; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008051:Lipid Bilayers; D008564:Membrane Potentials; D008745:Methylation; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002264:Carboxylic Acids; D008051:Lipid Bilayers; D015222:Sodium Channels; D000584:Amiloride