title: Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL.
abstract: We have used the patch-clamp technique to study the effect of dietary K intake on the apical K channels in the medullary thick ascending limb (mTAL) of rat kidneys. The channel activity, defined by the number of channels in a patch and the open probability (NPo), of the 30- and 70-pS K channels, was 0.18 and 0.11, respectively, in the mTAL from rats on a K-deficient diet. In contrast, NPo of the 30- and 70-pS K channels increased to 0.60 and 0.80, respectively, in the tubules from animals on a high-K diet. The concentration of 20-hydroxyeicosatetraenoic acid (20-HETE) measured with gas chromatography-mass spectrometry was 0.8 pg/microg protein in the mTAL from rats on a high-K diet and increased significantly to 4.6 pg/microg protein in the tubules from rats on a K-deficient diet. Addition of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17-ODYA), agents that inhibit the formation of 20-HETE, had no significant effect on the activity of the 30-pS K channels. However, DDMS/17-ODYA significantly increased the activity of the apical 70-pS K channel from 0.11 to 0.91 in the mTAL from rats on a K-deficient diet. In contrast, inhibition of the cytochrome P-450 metabolism of arachidonic acid increased NPo from 0.64 to 0.81 in the tubules from animals on a high-K diet. Furthermore, the sensitivity of the 70-pS K channel to 20-HETE was the same between rats on a high-K diet and on a K-deficient diet. Finally, the pretreatment of the tubules with DDMS increased NPo of the 70-pS K channels in the mTAL from rats on a K-deficient diet to 0.76. We conclude that an increase in 20-HETE production is involved in reducing the activity of the apical 70-pS K channels in the mTAL from rats on a K-deficient diet.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gu
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: M
authors.initials: M
authors.lastname: Balazy
authors.forename: W
authors.initials: W
authors.lastname: Wang
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology* / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D017419:Potassium, Dietary / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015221:Potassium Channels; D017419:Potassium, Dietary; D013450:Sulfones; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C117975:DDMS