The Na-K-Cl Co-transporter in astrocyte swelling

Metab Brain Dis. 2010 Mar;25(1):31-8. doi: 10.1007/s11011-010-9180-3. Epub 2010 Mar 25.


Ion channels, exchangers and transporters are known to be involved in cell volume regulation. A disturbance in one or more of these systems may result in loss of ion homeostasis and cell swelling. In particular, activation of the Na(+)-K(+)-Cl(-) cotransporters has been shown to regulate cell volume in many conditions. The Na(+)-K(+)-Cl- cotransporters (NKCC) are a class of membrane proteins that transport Na, K, and Cl ions into and out of a wide variety of epithelial and nonepithelial cells. Studies have established the role of NKCC1 in astrocyte swelling/brain edema in ischemia and trauma. Our recent studies suggest that NKCC1 activation is also involved in astrocyte swelling induced by ammonia and in the brain edema in the thioacetamide model of acute liver failure. This review will focus on mechanisms of NKCC1 activation and its contribution to astrocyte swelling/brain edema in neurological disorders, with particular emphasis on ammonia neurotoxicity and acute liver failure.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Ammonia / metabolism
  • Ammonia / toxicity
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Edema / metabolism*
  • Brain Edema / physiopathology
  • Cell Size
  • Disease Models, Animal
  • Hepatic Encephalopathy / metabolism*
  • Hepatic Encephalopathy / pathology
  • Hepatic Encephalopathy / physiopathology
  • Humans
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / complications
  • Liver Failure, Acute / physiopathology
  • Oxidative Stress / physiology
  • Sodium-Potassium-Chloride Symporters / genetics
  • Sodium-Potassium-Chloride Symporters / metabolism*
  • Solute Carrier Family 12, Member 2


  • SLC12A2 protein, human
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 2
  • Ammonia