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AT 2 R is involved in mediating the effect of high dietary K (HK) intake on basolateral Kir4.1 in the distal convoluted tubule (DCT)
Author(s) -
Wu Peng,
Gao Zhongxiuzi,
Wang Mingxiao,
Su XiaoTong,
Wang Lijun,
Wang WenHui
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.967.20
Subject(s) - distal convoluted tubule , endocrinology , chemistry , medicine , losartan , epithelial polarity , patch clamp , nephron , kidney , angiotensin ii , electrophysiology , cell , biochemistry , receptor
The basolateral 40–45 pS K channel in the DCT is composed of two inwardly‐rectifying K channels (Kir), Kir4.1 and Kir5.1. Previous study has demonstrated that Kir4.1 plays a predominant role in determining the basolateral K conductance in the DCT and that the inhibition of Kir4.1 leads to the suppression of NCC. In the present study, we used patch‐clamp experiments to examine the effect of HK intake on the basolateral Kir4.1/5.1 channels in the DCT of mouse kidney. Increased dietary K intake not only decreased the probability of finding the 40 pS K channel in the basolateral membrane of the DCT but also channel open probability. The notion that HK intake inhibits the basolateral Kir4.1 channels is also supported by measurement of Ba 2+ ‐sensitive whole cell K currents in DCT1. We observed that HK intake decreased the Ba 2+ ‐sensitive K currents in the DCT by more than 50% in comparison to that on control K diet. Because AT 2 R is expressed in the distal nephron and a HK intake stimulates AT 2 R expression, we examine whether AT 2 R is involved in mediating the effect of HK intake on basolateral K channels in the DCT with patch‐clamp technique. Under control conditions (normal K diet), neither angiotensin II (AngII) nor AngII + losartan has a significant effect on the 40 pS K channel in the DCT. In contrast, in animals kept on a HK diet for 7 days, inhibition of AT 1 R with losartan reduced basolateral K channel activity in the DCT (control NP o , 1.4 ± 0.3; losartan 0.85 ± 0.25). Moreover, application of 100 nM AngII caused an additional inhibition of the basolateral 40 pS K channel (NP o , 0.3 ± 0.1). To study the role of AT 2 R in mediating the effect of HK intake on the basolateral K channel in the DCT, we performed the patch‐clamp study in mice that were treated with PD123319 for 7 days through an osmotic micro pump. Inhibition of AT 2 R did not significantly affect the basolateral K currents in the mice on a normal K diet but it largely abolished the HK‐intake‐induced decrease in the basolateral K conductance of the DCT. This suggests a role for AT 2 R in mediating HK intake‐induced inhibition of Kir4.1/5.1 in the basolateral membrane of the DCT. We conclude that high K intake decreases the basolateral K conductance in the DCT and that AT 2 R is involved in mediating the effect of HK intake on the basolateral Kir4.1/5.1.