The electroneutral Na(+)-(K+)-Cl- cotransport family.
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.
Hebert
S C
SC
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Gamba
G
G
Kaplan
M
M
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D004563:Electrochemistry; D015640:Ion Channel Gating / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters
D002352:Carrier Proteins; D002712:Chlorides; D008565:Membrane Proteins; D028021:Sodium-Potassium-Chloride Symporters; D012964:Sodium; D011188:Potassium