Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC abundance changes with dietary NaCl restriction

Shyama Masilamani, Xiaoyan Wang, Gheun Ho Kim, Heddwen Brooks, Jakob Nielsen, Soren Nielsen, Kenzo Nakamura, John B. Stokes, Mark A. Knepper

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118 Scopus citations


We have used peptide-directed antibodies to each major renal Na transporter and channel proteins to screen renal homogenates for changes in Na transporter protein expression after initiation of dietary NaCl restriction. After equilibration on a NaCl-replete diet (2.0 meq·200 g body wt-1·day-1), rats were switched to a NaCl-deficient diet (0.02 meq·200 g body wt-1·day-1). Na excretion fell to 25% of baseline levels on day 1, followed by a further decrease <4% of baseline levels on day 3, of NaCl restriction. The decreased Na excretion at day 1 occurred despite the absence of a significant increase in plasma aldosterone level or in the abundance of any of the major renal Na transporters. However, after a 1-day lag, plasma aldosterone levels increased in association with increases in abundances of three aldosterone-regulated Na transporter proteins: the thiazide-sensitive Na-Cl cotransporter (NCC), the α-subunit of the amiloride-sensitive epithelial Na channel (α-ENaC), and the 70-kDa form of γ-ENaC. RNase protection assays of transporter mRNA levels revealed an increase in renal α-ENaC mRNA coincident with the increase in α-ENaC protein abundance. However, there was no change in NCC mRNA abundance, suggesting that the increase in NCC protein in response to dietary NaCl restriction was not a result of altered gene transcription. These results point to early regulatory processes that decrease renal Na excretion without an increase in the abundance of any Na transporter, followed by a late aldosterone-dependent response associated with upregulation of NCC and ENaC.

Original languageEnglish (US)
Pages (from-to)F648-F657
JournalAmerican Journal of Physiology - Renal Physiology
Issue number4 52-4
StatePublished - Oct 2002


  • Aldosterone
  • Bumetanide-sensitive type 2 sodium-potassium-2 chloride cotransporter
  • Collecting duct
  • Distal convoluted tubule
  • Epithelial sodium channel
  • Thiazide-sensitive sodium-chloride cotransporter
  • Type 3 sodium/hydrogen exchanger

ASJC Scopus subject areas

  • Physiology
  • Urology


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