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Effect of knocking out receptor protein tyrosine phosphatase γ (RPTPγ) in the HCO 3 ‐induced inhibition of HCO 3 reabsorption by mouse renal proximal tubules
Author(s) -
Zhou Yuehan
Publication year - 2010
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.24.1_supplement.1024.8
Subject(s) - chemistry , reabsorption , medicine , endocrinology , microbiology and biotechnology , kidney , biology
The accompanying abstract shows that knocking out RPTPγ renders isolated perfused proximal tubules (PTs) incapable of responding to changes in basolateral (BL) [CO 2 ], consistent with the hypothesis that the “orphaned” RPTPγ is a CO 2 sensor. Here I test the hypothesis that RPTPγ is also a HCO 3 sensor. I perfused PTs from wild‐type vs RPTPγ‐null mice, using out‐of‐equilibrium to vary [HCO 3 ] BL at fixed [CO 2 ] BL and pH BL . In wild‐type PTs, raising [HCO 3 ] BL from 0 to 22 (“baseline”) to 44 mM (fixed [CO 2 ] BL = 5%, pH BL = 7.4) decreased J HCO 3 from 222 ± 12 (n = 14) to 136 ± 7 (n = 40) to 55 ± 12 pmol mm −1 min −1 (“pmm”, n = 14). In RPTPγ‐null PTs, baseline J HCO 3 was reduced by 23% to 105 ± 7 pmm (p = 0.002, 1‐way ANOVA), and the responses to 0 mM [HCO 3 ] BL ( J HCO 3 = 112 ± 6, n = 6) and 44 mM [HCO 3 ] BL ( J HCO 3 = 100 ± 8, n = 6) were eliminated. Finally, when I added 10 −8 M candesartan (non‐peptide AT 1 antagonist) to the lumen of RPTPγ‐null PTs, baseline J HCO 3 further fell by 29% to the “pedestal” level ( J HCO 3 75 ± 8 pmm, n = 18, p = 0.012, 1‐way ANOVA). Moreover, the responses to 0 mM [HCO 3 ] BL ( J HCO 3 = 67 ± 14, n = 4) and 44 mM [HCO 3 ] BL ( J HCO 3 = 55 ± 6, n = 5) were eliminated. Thus, knocking out RPTPγ eliminates the PT response to changes in [HCO 3 ] BL , consistent with the idea that RPTPγ is a HCO 3 sensor, perhaps reporting the ratio [CO 2 ] BL /[HCO 3 ] BL , as part of a signal‐transduction cascade that also includes the apical AT 1 receptor.