The electroneutral Na(+)-(K+)-Cl- cotransport family

Kidney Int. 1996 Jun;49(6):1638-41. doi: 10.1038/ki.1996.238.


Recently the molecular identification of the major electroneutral sodium-potassium-chloride entry mechanisms present on apical membranes of distal nephron segments of the mammalian kidney, on basolateral membranes of many non-renal epithelial cells and on certain non-epithelial tissues has been achieved. These transporters represent a major pathway for cellular uptake of chloride critical for chloride absorptive and secretory processes and for cell volume regulation following cell shrinkage. In the mammalian kidney, these sodium-coupled chloride cotransporters represent the major target sites for clinically useful diuretics including the "loop" diuretics [furosemide (Lasix) and bumetanide (Bumex)] and thiazides (such as, chlorothiazide, hydrochlorothiazide and metolazone). Although these Na-(K)-Cl cotransporters exhibit functional and pharmacological differences, they clearly evolved from a common ancestral gene and thus form a new gene family. This information is already advancing our understanding of the evolution, structure and function of these transporters both in renal handling of sodium and in hypertension.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / physiology*
  • Chlorides / metabolism
  • Electrochemistry
  • Ion Channel Gating / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology
  • Potassium / metabolism
  • Sodium / metabolism
  • Sodium-Potassium-Chloride Symporters


  • Carrier Proteins
  • Chlorides
  • Membrane Proteins
  • Sodium-Potassium-Chloride Symporters
  • Sodium
  • Potassium