PMID- 32845718
OWN - NLM
STAT- MEDLINE
DCOM- 20201217
LR  - 20231213
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 319
IP  - 4
DP  - 2020 Oct 1
TI  - Coordinate adaptations of skeletal muscle and kidney to maintain extracellular 
      [K(+)] during K(+)-deficient diet.
PG  - C757-C770
LID - 10.1152/ajpcell.00362.2020 [doi]
AB  - 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 
      alpha2-beta2 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 mumol K(+) 
      into the urine and muscle shifts ~47 mumol K(+) from ICF to ECF, illustrating the 
      importance of the concerted responses during K(+) deficiency.
FAU - McFarlin, Brandon E
AU  - McFarlin BE
AUID- ORCID: 0000-0003-3829-4609
AD  - Department of Physiology and Neuroscience, Keck School of Medicine of the 
      University of Southern California, Los Angeles, California.
FAU - Chen, Yuhan
AU  - Chen Y
AD  - Division of Clinical Pharmacology, Vanderbilt University Medical Center, 
      Nashville, Tennessee.
AD  - Department of Cardiology, Nanjing University Medical School, Nanjing, China.
FAU - Priver, Taylor S
AU  - Priver TS
AD  - Department of Physiology and Neuroscience, Keck School of Medicine of the 
      University of Southern California, Los Angeles, California.
FAU - Ralph, Donna L
AU  - Ralph DL
AD  - Department of Physiology and Neuroscience, Keck School of Medicine of the 
      University of Southern California, Los Angeles, California.
FAU - Mercado, Adriana
AU  - Mercado A
AUID- ORCID: 0000-0002-6881-0160
AD  - Department of Nephrology, Instituto Nacional de Cardiologia Ignacio Chavez, 
      Mexico City, Mexico.
FAU - Gamba, Gerardo
AU  - Gamba G
AD  - Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad 
      Nacional Autonoma de Mexico and Instituto Nacional de Ciencias Medicas y 
      Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Madhur, Meena S
AU  - Madhur MS
AD  - Division of Clinical Pharmacology, Vanderbilt University Medical Center, 
      Nashville, Tennessee.
FAU - McDonough, Alicia A
AU  - McDonough AA
AUID- ORCID: 0000-0002-0459-469X
AD  - Department of Physiology and Neuroscience, Keck School of Medicine of the 
      University of Southern California, Los Angeles, California.
LA  - eng
GR  - DP2 HL137166/HL/NHLBI NIH HHS/United States
GR  - R01 DK083785/DK/NIDDK NIH HHS/United States
GR  - 2R01DK083785/HHS | NIH | National Institute of Diabetes and Digestive and Kidney 
      Diseases (NIDDK)/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200826
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Kcnj10 (channel))
RN  - 0 (Osr1 protein, mouse)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 0 (Symporters)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.- (Stk39 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Adaptation, Physiological/*genetics
MH  - Animals
MH  - Blood Pressure/genetics
MH  - Epithelial Sodium Channels/genetics
MH  - Extracellular Fluid/metabolism
MH  - Humans
MH  - Hypertension/*genetics/pathology
MH  - Kidney/*metabolism/pathology
MH  - Mice
MH  - Muscle, Skeletal/metabolism/pathology
MH  - Phosphorylation/genetics
MH  - Potassium/*metabolism
MH  - Potassium Channels, Inwardly Rectifying/genetics
MH  - Protein Serine-Threonine Kinases/genetics
MH  - Sodium-Potassium-Chloride Symporters/genetics
MH  - Solute Carrier Family 12, Member 2/genetics
MH  - Symporters/genetics
MH  - Transcription Factors/genetics
MH  - K Cl- Cotransporters
PMC - PMC7654654
OTO - NOTNLM
OT  - KCC3
OT  - NCC
OT  - NKCC1
OT  - NKCC2
OT  - sodium pump alpha2-beta2
COIS- No conflicts of interest, financial or otherwise, are declared by the author(s).
EDAT- 2020/08/28 06:00
MHDA- 2020/12/18 06:00
PMCR- 2021/10/01
CRDT- 2020/08/27 06:00
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2020/12/18 06:00 [medline]
PHST- 2020/08/27 06:00 [entrez]
PHST- 2021/10/01 00:00 [pmc-release]
AID - C-00362-2020 [pii]
AID - 10.1152/ajpcell.00362.2020 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2020 Oct 1;319(4):C757-C770. doi: 
      10.1152/ajpcell.00362.2020. Epub 2020 Aug 26.