Coordinate adaptations of skeletal muscle and kidney to maintain extracellular [K(+)] during K(+)-deficient diet.

Extracellular fluid (ECF) potassium concentration ([K(+)]) is maintained by adaptations of kidney and skeletal muscle, responses heretofore studied separately. We aimed to determine how these organ systems work in concert to preserve ECF [K(+)] in male C57BL/6J mice fed a K(+)-deficient diet (0K) versus 1% K(+) diet (1K) for 10 days (n = 5-6/group). During 0K feeding, plasma [K(+)] fell from 4.5 to 2 mM; hindlimb muscle (gastrocnemius and soleus) lost 28 mM K(+) (from 115 ± 2 to 87 ± 2 mM) and gained 27 mM Na(+) (from 27 ± 0.4 to 54 ± 2 mM). Doubling of muscle tissue [Na(+)] was not associated with inflammation, cytokine production or hypertension as reported by others. Muscle transporter adaptations in 0K- versus 1K-fed mice, assessed by immunoblot, included decreased sodium pump α2-β2 subunits, decreased K(+)-Cl(-) cotransporter isoform 3, and increased phosphorylated (p) Na(+),K(+),2Cl(-) cotransporter isoform 1 (NKCC1p), Ste20/SPS-1-related proline-alanine rich kinase (SPAKp), and oxidative stress-responsive kinase 1 (OSR1p) consistent with intracellular fluid (ICF) K(+) loss and Na(+) gain. Renal transporters' adaptations, effecting a 98% reduction in K(+) excretion, included two- to threefold increased phosphorylated Na(+)-Cl(-) cotransporter (NCCp), SPAKp, and OSR1p abundance, limiting Na(+) delivery to epithelial Na(+) channels where Na(+) reabsorption drives K(+) secretion; and renal K sensor Kir 4.1 abundance fell 25%. Mass balance estimations indicate that over 10 days of 0K feeding, mice lose ~48 μmol K(+) into the urine and muscle shifts ~47 μmol K(+) from ICF to ECF, illustrating the importance of the concerted responses during K(+) deficiency.