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10.1681/ASN.2014070658

http://scihub22266oqcxt.onion/10.1681/ASN.2014070658
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25848073!4625665!25848073
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suck abstract from ncbi


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pmid25848073      J+Am+Soc+Nephrol 2015 ; 26 (11): 2678-90
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  • Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport #MMPMID25848073
  • Wang L; Zhang C; Su X; Lin DH; Wang W
  • J Am Soc Nephrol 2015[Nov]; 26 (11): 2678-90 PMID25848073show ga
  • Kcnj10 encodes the inwardly rectifying K(+) channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K(+) channel are incompletely characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells demonstrated that c-Src-induced stimulation of Kcnj10 requires coexpression of caveolin-1 (cav-1), and immunostaining showed expression of cav-1 in the basolateral membrane of parvalbumin-positive DCT. Patch-clamp experiments detected a 40-pS inwardly rectifying K(+) channel, a heterotetramer of Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild-type (WT) and cav-1-knockout (KO) mice. However, the activity of this basolateral 40-pS K(+) channel was lower in KO mice than in WT mice. Moreover, the K(+) reversal potential (an indication of membrane potential) was less negative in the DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated that cav-1 deficiency decreased the expression of the Na(+)/Cl(-) cotransporter and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of epithelial Na(+) channel-alpha. Furthermore, the urinary excretion of Mg(2+) and K(+) was significantly higher in KO mice than in WT mice, and KO mice developed hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav-1 decreases basolateral K(+) channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na(+)/Cl(-) cotransporter expression induced by cav-1 deficiency may underlie the compromised renal transport of Mg(2+), Ca(2+), and K(+).
  • |Animals[MESH]
  • |Calcium/metabolism[MESH]
  • |Caveolin 1/genetics/*physiology[MESH]
  • |Cell Membrane/metabolism[MESH]
  • |Electrolytes[MESH]
  • |Female[MESH]
  • |Gitelman Syndrome/metabolism[MESH]
  • |Green Fluorescent Proteins/metabolism[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Hypokalemia/metabolism[MESH]
  • |Kidney/metabolism[MESH]
  • |Magnesium/*metabolism[MESH]
  • |Male[MESH]
  • |Membrane Potentials[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mice, Knockout[MESH]
  • |Microscopy, Fluorescence[MESH]
  • |Patch-Clamp Techniques[MESH]
  • |Potassium Channels, Inwardly Rectifying/*metabolism[MESH]
  • |Potassium/*metabolism[MESH]


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