title: Adaptive downregulation of a quinidine-sensitive cation conductance in renal principal cells of TWIK-1 knockout mice.
abstract: TWIK-1, a member of the two-pore domain K(+) channel family, is expressed in brain, kidney, and lung. The aim of this study was to examine the effect of loss of TWIK-1 on the renal cortical collecting duct. Ducts were isolated from wild-type and TWIK-1 knockout mice by enzyme digestion and whole-cell clamp obtained via the basolateral membrane. Current- and voltage-clamp approaches were used to examine K(+) conductances. No difference was observed between intercalated cells from wild-type or knockout ducts. In contrast, knockout principal cells were hyperpolarized compared to wild-type cells and had a reduced membrane conductance. This was a consequence of a fall in a barium-insensitive, quinidine-sensitive conductance (G (Quin)). G (Quin) demonstrated outward rectification and had a relatively low K(+) to Na(+) selectivity ratio. Loss of G (Quin) would be expected to lead to the hyperpolarization observed in knockout ducts by increasing fractional K(+) conductance and Na(+) uptake by the cell. Consistent with this hypothesis, knockout ducts had an increased diameter in comparison to wild-type ducts. These data suggest that G (Quin) contributes to the resting membrane potential in the cortical collecting duct and that a fall in G (Quin) could be an adaptive response in TWIK-1 knockout ducts.
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: I D
authors.initials: ID
authors.lastname: Millar
authors.forename: H C
authors.initials: HC
authors.lastname: Taylor
authors.forename: G J
authors.initials: GJ
authors.lastname: Cooper
authors.forename: J D
authors.initials: JD
authors.lastname: Kibble
authors.forename: J
authors.initials: J
authors.lastname: Barhanin
authors.forename: L
authors.initials: L
authors.lastname: Robson
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001464:Barium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011802:Quinidine; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002412:Cations; C486372:Kcnk1 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D001464:Barium; D011802:Quinidine; D011188:Potassium