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Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Renal+Physiol 2020 ; 318 (6): F1369-F1376 Nephropedia Template TP
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Epoxyeicosatrienoic acid metabolites inhibit Kir4 1/Kir5 1 in the distal convoluted tubule #MMPMID32308018
Wang MX; Wang LJ; Xiao Y; Zhang DD; Duan XP; Wang WH
Am J Physiol Renal Physiol 2020[Jun]; 318 (6): F1369-F1376 PMID32308018show ga
Cytochrome P-450 (Cyp) epoxygenase-dependent metabolites of arachidonic acid (AA) have been shown to inhibit renal Na(+) transport, and inhibition of Cyp-epoxygenase is associated with salt-sensitive hypertension. We used the patch-clamp technique to examine whether Cyp-epoxygenase-dependent AA metabolites inhibited the basolateral 40-pS K(+) channel (Kir4.1/Kir5.1) in the distal convoluted tubule (DCT). Application of AA inhibited the basolateral 40-pS K(+) channel in the DCT. The inhibitory effect of AA on the 40-pS K(+) channel was specific because neither linoleic nor oleic acid was able to mimic the effect of AA on the K(+) channel. Inhibition of Cyp-monooxygenase with N-methylsulfonyl-12,12-dibromododec-11-enamide or inhibition of cyclooxygenase with indomethacin failed to abolish the inhibitory effect of AA on the 40-pS K(+) channel. However, the inhibition of Cyp-epoxygenase with N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide abolished the effect of AA on the 40-pS K(+) channel in the DCT. Moreover, addition of either 11,12-epoxyeicosatrienoic acid (EET) or 14,15-EET also inhibited the 40-pS K(+) channel in the DCT. Whole cell recording demonstrated that application of AA decreased, whereas N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide treatment increased, Ba(2+)-sensitive K(+) currents in the DCT. Finally, application of 14,15-EET but not AA was able to inhibit the basolateral 40-pS K(+) channel in the DCT of Cyp2c44(-/-) mice. We conclude that Cyp-epoxygenase-dependent AA metabolites inhibit the basolateral Kir4.1/Kir5.1 in the DCT and that Cyp2c44-epoxygenase plays a role in the regulation of the basolateral K(+) channel in the mouse DCT.