Response of intercalated cell BKα knock‐out mice to a high K diet
Bibliographic record
Abstract
Flow‐induced K secretion (FIKS) in the cortical collecting duct (CCD) is mediated by apical Ca2+−/stretch‐activated BK channels. These channels also contribute to the renal adaptation to dietary K intake. BK channels are expressed in both intercalated (ICs) and principal cells (PCs) in CCDs. Several lines of evidence suggest that BK channels in ICs are responsible for FIKS: (i) the density of BK channels in ICs exceeds that in PCs and (ii) dietary K loading upregulates BKα expression predominantly in the apical membrane of ICs in rabbit CCDs. We generated a mouse with targeted deletion of BKα, the pore forming subunit of the BK channel, in ICs (IC‐BKα‐KO) by crossing floxed BKα mice with B1 V‐ATPase Cre mice, after confirming that the B1 Cre was expressed primarily in ICs in the kidney. As the targeted deletion in exon 7 of the BKα sequence was not expected to lead to a frame shift, immunodetectable BKα was identified in ICs of IC‐BKα‐KO CCDs using an antibody directed against the BKα C terminus. Perforated whole‐cell recordings performed at +60 mV in 7 CCD ICs in an IC‐BKα‐KO fed a HK diet revealed that 4 ICs had no BK currents and 3 ICs had low charybdotoxin‐sensitive K currents (37, 65, 90 pA) vs. readily detectable currents in 2 ICs in WT mice fed a control K diet (600–800 pA). IC‐BKα‐KO and floxed controls were fed a HK diet × 10 days to maximize BK channel expression and received isotonic saline IP to induce a high urine flow rate. Over 6 hr following volume expansion, rates of urinary Na (39.1±11.1 vs. 36.0±15.2 μmol/hr) and K (165.5±50.1 vs. 171.9±76.0 μmol/hr) excretion were similar in IC‐BKα‐KO (n=10) and floxed (n=17) mice of both sexes. KO mice exhibited a higher blood [K] (5.5±0.8 vs. 5.0±0.7 mM; p<0.05) and BUN (25.3±5.7 vs. 20.6±5.1 mg/dL; p<0.03) vs. floxed controls although BW did not differ (21.0±2.7 vs. 22.6±3.4. gm, respectively). The difference in blood [K] between male IC‐BKα‐KO and floxed mice was highly significant (5.7±0.7 vs. 5.0±0.7 mM; n=14 and 16, p<0.02). In the absence of volume expansion, rates of urinary Na (1.3±0.8 vs. 1.3±1.3 μmol/hr) and K (50.9±23.7 vs. 40.4±22.5 μmol/hr) excretion were similar in the two groups over a 6 hr period (n=9 and 15, respectively). These results suggest that in the absence of IC BKα, mice have a limited capacity for adaptation to a HK diet, as evidenced by the higher blood [K], but still demonstrate FIKS. Support or Funding Information K08 DK110332, P30 DK079307, R01 DK038470, R01 DK098145, I01 BX002510 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".