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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Renal+Physiol 2017 ; 313 (2): F254-F261 Nephropedia Template TP
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PGF(2alpha) regulates the basolateral K channels in the distal convoluted tubule #MMPMID28356287
Wang L; Zhang C; Su XT; Lin DH; Wu P; Schwartzman ML; Wang WH
Am J Physiol Renal Physiol 2017[Aug]; 313 (2): F254-F261 PMID28356287show ga
Our aim is to examine the role of PGF(2alpha) receptor (FP), a highly expressed prostaglandin receptor in the distal convoluted tubule (DCT) in regulating the basolateral 40-pS K channel. The single-channel studies demonstrated that PGF(2alpha) had a biphasic effect on the 40-pS K channel in the DCT-PGF(2alpha) stimulated at low concentrations (less than 500 nM), while at high concentrations (above 1 microM), it inhibited the 40-pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF(2alpha) (a metabolite of PGF(2alpha)) nor PGE(2) was able to mimic the effect of PGF(2alpha) on the 40-pS K channel in the DCT. The inhibition of PKC had no significant effect on the 40-pS K channel; however, it abrogated the inhibitory effect of 5 microM PGF(2alpha) on the K channel. Moreover, stimulation of PKC inhibited the 40-pS K channel in the DCT, suggesting that PKC mediates the inhibitory effect of PGF(2alpha) on the 40-pS K channel. Conversely, the stimulatory effect of PGF(2alpha) on the 40-pS K channel was absent in the DCT treated with DPI, a NADPH oxidase (NOX) inhibitor. Also, adding 100 microM H(2)O(2) mimicked the stimulatory effect of PGF(2alpha) and increased the 40-pS K channel activity in DCT. Moreover, the stimulatory effect of 500 nM PGF(2alpha) and H(2)O(2) was not additive, suggesting the role of superoxide-related species in mediating the stimulatory effect of PGF(2alpha) on the 40-pS K channel. The inhibition of Src family tyrosine protein kinase (SFK) not only inhibited the 40-pS K channel in the DCT but also completely abolished the stimulatory effects of PGF(2alpha) and H(2)O(2) on the 40-pS K channel. We conclude that PGF(2alpha) at low doses stimulates the basolateral 40-pS K channel by a NOX- and SFK-dependent mechanism, while at high concentrations, it inhibits the K channel by a PKC-dependent pathway.