Thick ascending limb: the Na(+):K (+):2Cl (-) co-transporter, NKCC2, and the calcium-sensing receptor, CaSR.
The thick ascending limb of Henle's loop is a nephron segment that is vital to the formation of dilute and concentrated urine. This ability is accomplished by a consortium of functionally coupled proteins consisting of the apical Na(+):K(+):2Cl(-) co-transporter, the K(+) channel, and basolateral Cl(-) channel that mediate electroneutral salt absorption. In thick ascending limbs, salt absorption is importantly regulated by the calcium-sensing receptor. Genetic or pharmacological disruption impairing the function of any of these proteins results in Bartter syndrome. The thick ascending limb is also an important site of Ca(2+) and Mg(2+) absorption. Calcium-sensing receptor activation inhibits cellular Ca(2+) absorption induced by parathyroid hormone, as well as passive paracellular Ca(2+) transport. The present review discusses these functions and their genetic and molecular regulation.
Gamba
Gerardo
G
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. gamba@biomedicas.unam.mx
Friedman
Peter A
PA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001477:Bartter Syndrome / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006973:Hypertension / Q000235:genetics; D007700:Kinetics; D008138:Loop of Henle / Q000378:metabolism*; D008969:Molecular Sequence Data; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D064466:Solute Carrier Family 12, Member 1
D002413:Cations, Divalent; C086989:KCNJ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D044169:Receptors, Calcium-Sensing; C578714:SLC12A1 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D019204:GTP-Binding Proteins; D002118:Calcium