期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 18, 期 7, 页码 2037-2045出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2006121333
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资金
- NHLBI NIH HHS [P01 HL034300, P01 HL034300-240009] Funding Source: Medline
- NIDDK NIH HHS [DK54983, R01 DK047402, R01 DK054983-08, DK47402, R01 DK054983] Funding Source: Medline
Previous study has demonstrated that superoxide and the related products are involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity in the cortical collecting duct (CCD). This study investigated the role of gp91(phox)-containing NADPH oxidase (NOXII) in mediating the effect of low K intake on renal K excretion and ROM K channel activity in gp91 (-/-) mice. K depletion increased superoxide levels, phosphorylation of c-Jun, expression of c-Src, and tyrosine phosphorylation of ROMK in renal cortex and outer medulla in wild-type (WT) mice. In contrast, tempol treatment in WT mice abolished whereas deletion of gp91 significantly attenuated the effect of low K intake on superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine phosphorylation of ROMK. Patch-clamp experiments demonstrated that low K intake decreased mean product of channel number (N) and open probability (P) (NPo) of ROMK channels from 1.1 to 0.4 in the CCD. However, the effect of low K intake on ROMK channel activity was significantly attenuated in the CCD from gp91 (-/-) mice and completely abolished by tempol treatment. Immunocytochemical staining also was used to examine the ROMK distribution in WT, gp91(-/-), and WT mice with tempol treatment in response to K restriction. K restriction decreased apical staining of ROMK in WT mice. In contrast, a sharp apical ROMK staining was observed in the tempol-treated WT or gp91 (-/-) mice. Metabolic cage study further showed that urinary K loss is significantly higher in gp91 (-/-) mice than in WT mice. It is concluded that superoxide anions play a key role in suppressing K secretion during K restriction and that NOXII is involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity.
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