| Autor: |
McFarlin BE; Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, California., Chen Y; Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.; Department of Cardiology, Nanjing University Medical School, Nanjing, China., Priver TS; Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, California., Ralph DL; Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, California., Mercado A; Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico., Gamba G; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Madhur MS; Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee., McDonough AA; Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, California. |
| Abstrakt: |
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. |
