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Adaptation to K + deficiency in mouse: coordinate regulation of muscle and kidney electrolyte transporters
Author(s) -
McFarlin Brandon E,
Chen Yuhan,
Madhur Meenakshi S,
Ralph Donna L,
McDonough Alicia A
Publication year - 2019
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.2019.33.1_supplement.575.3
Subject(s) - medicine , endocrinology , chemistry , excretion , sodium , urine , extracellular fluid , kidney , urinary system , extracellular , biology , biochemistry , organic chemistry
Our previous work in rats subjected to K + deficient diets demonstrated that K + shifts from muscle intracellular fluid (ICF) stores to extracellular fluid (ECF) compartment in order to buffer the fall in ECF K + due to finite losses in urine and feces. The aim of this study was to determine the coordinated renal and muscle adaptations to preserve K + and Na + homeostasis during a K + deficient diet in mice. Methods Male C57BL/6 mice were fed control (1K) or K + deficient (0K) diets for 10 days. Urine was collected overnight at 6 days in metabolic cages. Kidney and muscle were collected at 10 days. [Na + ] and [K + ] were determined by flame photometry in plasma, urine and muscle (mixed gastrocnemius + soleus) extracts. Transporter abundance was assessed by quantitative immunoblot. Results Plasma [K + ] fell from 4.8 ± 0.3 (1K) to 2.3 ± 0.3 mM (0K) and plasma [Na + ] was maintained at 148.6 ±1.5 mM (0K). K + deficient diet reduced muscle [K + ] from 125 ± 2 (1K) to 92 ± 5 mM (0K) and doubled muscle [Na + ] from 30 ± 1 (1K) to 61 ± 1 mM (0K), expressed as tissue wet weight. 0K diet also reduced muscle Na, K‐ATPase α2 and β2 subunit abundance by 35 and 60%, respectively, consistent with the measured K + loss and Na + gain. Urinary K + excretion fell from 0.19 ± 0.1 (1K) to 0.003 ± 0.001 mmol (0K) while urinary Na + was not significantly altered by 0K indicative of adaptations to conserve K + and maintain Na + . Renal sodium transporters changed as follows during K + deficient diet: proximal tubule Na/H exchanger (NHE3) decreased 35% while NHE3pS552 increased 1.5 fold consistent with lower NHE3 activity; distal tubule Na‐Cl co‐transporter (NCC) phosphorylated at T53 and S71 both increased >1.5 fold, consistent with higher distal tubule Na + reabsorption; epithelial Na + channel gamma subunit (ENaCγ) increased >1.5 fold (no cleavage), consistent with accumulation of inactive ENaC. Summary During restricted potassium intake in mice, muscle donates K + to ECF facilitated by reducing Na, K‐ATPase abundance, and NCC covalent modification coupled with reduced ENaC activity reduces the driving force for K + secretion. These responses help blunt the fall in plasma [K + ], a key determinant of membrane potential. Reduced proximal Na + reabsorption via NHE3 may drive a tubuloglomerular feedback mediated reduction in GFR to reduce urinary K + losses. Despite the increase in muscle [Na + ] and decrease in proximal Na + transport there was no evidence for significant changes in sodium excretion. Support or Funding Information DK083785 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .