Differential gene regulation of renal salt entry pathways by salt load in the distal nephron of the rat

Pflugers Arch. 2001 Jul;442(4):498-504. doi: 10.1007/s004240100544.

Abstract

The aim of the present study was to determine the molecular responses of the main salt-reabsorbing systems in the distal nephron to changes of salt load of the organism. For this purpose we analysed messenger ribonucleic acid (mRNA) levels for the bumetanide-sensitive Na+K+2Cl- cotransporter (BSC1), the thiazide-sensitive Na+Cl- cotransporter (TSC), the kidney-specific inwards rectifier K+ channel (ROMK), the amiloride-sensitive epithelial Na+ channel (ENaC) and the kidney-specific Cl- channel ClC-K2, in the cortex and inner and outer medulla of kidneys from male Sprague-Dawley rats fed a high- (8% w/w), normal- (0.6%) or low-(0.02%) salt diet or treated chronically with subcutaneous infusions of furosemide (12 mg/kg per day). BSC1 and ROMK mRNA levels did not differ between the four treatment groups. TSC mRNA increased during furosemide treatment 1.75-fold versus control but was not affected by a high- or a low-salt diet. The mRNA for the alpha-subunit of ENaC increased with the low-salt diet (about 1.5-fold) and with furosemide (about 2.1-fold) in all kidney zones, but did not change with the high-salt diet. Dietary salt loading down-regulated CIC-K2 mRNA in the outer medulla 0.6-fold versus control whilst furosemide treatment, but not the low-salt diet, increased ClC-K2 mRNA in the outer (1.6-fold) and inner medulla (2.0-fold). These findings suggest that gene expression of Na+ and Cl- entry pathways in the distal nephron are at least partly regulated by the salt load of the organism, such that salt-reabsorbing systems are stimulated by salt deficiency and suppressed by salt overload.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Chloride Channels / genetics
  • Epithelial Sodium Channels
  • Gene Expression Regulation / physiology*
  • Kidney Cortex / physiology
  • Kidney Medulla / physiology
  • Male
  • Nephrons / physiology*
  • Potassium Channels / genetics
  • Potassium Channels, Inwardly Rectifying*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / genetics
  • Sodium Channels / genetics
  • Sodium Chloride Symporters
  • Sodium Chloride, Dietary / pharmacokinetics*
  • Sodium-Potassium-Chloride Symporters / genetics
  • Solute Carrier Family 12, Member 1
  • Solute Carrier Family 12, Member 3
  • Symporters*
  • Water-Electrolyte Balance / physiology*

Substances

  • Carrier Proteins
  • Chloride Channels
  • ClC-2 chloride channels
  • Epithelial Sodium Channels
  • Kcnj1 protein, rat
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • RNA, Messenger
  • Receptors, Drug
  • Slc12a1 protein, rat
  • Slc12a3 protein, rat
  • Sodium Channels
  • Sodium Chloride Symporters
  • Sodium Chloride, Dietary
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 1
  • Solute Carrier Family 12, Member 3
  • Symporters
  • thiazide receptor