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Renal handling of potassium in the type 2 Bartter's mouse on a low Na, high K diet (LNaHK)
Author(s) -
WangFrance Jun,
Wang Bangchen,
Li Huaqing,
Sansom Steven
Publication year - 2017
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.31.1_supplement.857.13
Subject(s) - endocrinology , medicine , chemistry , aldosterone , reabsorption , nephron , epithelial sodium channel , renal sodium reabsorption , homeostasis , kidney , potassium , sodium , urine flow rate , tubular fluid , renal function , biology , organic chemistry
Mice on a low Na, high K diet (LNaHK; 0.01% Na, 5% K, 5% carbonate/citrate/Cl) maintain K balance because of the dietary effect to stimulate high distal flow and elicit a very high plasma aldosterone (P[aldo]) that maximally increases the activity of the epithelial Na channel (ENaC). Presumably, the high distal flow stimulates K secretion by the large, Ca‐activated K channel (BK) while the enhanced ENaC‐mediated Na reabsorption increases the driving force for K secretion via both BK and the renal outer medullary K channel (ROMK). However, the notion that ROMK plays a role in K secretion in the distal nephron of mice on LNaHK has not been examined in ROMK knockout mice (KO). To this end, we determined plasma aldosterone levels (P[aldo]; ELISA) and studied the renal handling of K in WT and KO (129/SvJ) mice on LNaHK (4–7 days) with metabolic cage experiments. Glomerular filtration rate (GFR) was measured with FITC‐inulin in conscious mice. On a control diet, there was no difference between WT and KO in the rate of K excretion (UKV; 516.1±63.4 and 521.3±64.1 mmol/day). On LNaHK, the UKV in KO was slightly but significantly lower than WT (1867±312.8 and 2483±92.1 mmol/day). Compared with WT on a control diet (0.3% Na, 0.6% K), KO exhibited a 4‐fold greater urine volume (KO = 5.4±0.6 and WT = 1.4±0.2 ml/day), a reduction in urine osmolality (658±63 and 3253±402 mOsm) but no change in plasma K (P[K]; 4.7±0.8 and 4.5±0.2 mM). Compared to WT on LNaHK, KO exhibited a higher urine volume (6.2±0.6 and 4.3±0.4 ml/day), a reduction in urine osmolality (660±43 and 1708±139 mOsm) but a reduced GFR (177.6±34.1 and 452.9±28.1 ml/day). The reduced GFR of KO was probably the result of a failure to retain Na and volume with a 2‐fold urinary Na loss (UNaV) compared with WT (64.9±11 and 30.8±4.1 mmol/day) and a three‐fold greater P[aldo] (9558±75 and 3717±470 pg/ml). However, KO on LNaHK still maintained K balance with a slightly, but not significantly, elevated P[K] (5.6±0.7 and 4.9±0.2 mM), a 2‐fold increased fractional excretion of K (193.8±52.1% and 97.7±8.0%) and a similar transtubular K gradients (TTKG; 27.4±2.8 and 26.3±1.4), compared with WT. These data indicate that reduced K excretion in KO on LNaHK is caused by reduced GFR due to inadequate Na and volume retention. ROMK of the aldosterone‐sensitive distal nephron does not contribute to K secretion of mice on LNaHK to maintain K balance. Support or Funding Information This project is supported by NIDDK grants 3451702067001 and 3451702071006.