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Sodium-potassium-chloride cotransport.

J M Russell1

  • 1Department of Biology, Biological Research Laboratories, Syracuse, New York, USA. jrussell@mailbox.syr.,edu

Physiological Reviews
|January 5, 2000
PubMed
Summary

The Na(+)-K(+)-Cl(-) cotransporter (NKCC) moves ions across cell membranes, maintaining crucial intracellular chloride levels for salt transport and neural function. Its roles in cell volume regulation and the cell cycle are under investigation.

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Area of Science:

  • Cellular Physiology
  • Molecular Biology
  • Biochemistry

Background:

  • The Na(+)-K(+)-Cl(-) cotransporter (NKCC) is a ubiquitous membrane transport mechanism found in nearly all animal cell types.
  • Two isoforms, NKCC1 and NKCC2, are known, with NKCC2 having multiple splice variants exclusive to the kidney, while NKCC1 is widely distributed.
  • NKCC maintains intracellular chloride concentration ([Cl(-)](i)) above electrochemical equilibrium, impacting epithelial salt transport and neuronal synaptic potentials.

Purpose of the Study:

  • To review the current understanding of the structure, function, and regulation of the Na(+)-K(+)-Cl(-) cotransporter (NKCC).
  • To explore the role of NKCC in maintaining intracellular chloride levels and its implications for cellular processes.
  • To discuss evidence regarding the stoichiometry, ATP dependence, and regulatory mechanisms of NKCC.

Main Methods:

  • Review of existing literature on NKCC function, structure, and regulation.
  • Analysis of evidence for NKCC's role in ion transport, cell volume, and cell cycle.
  • Discussion of experimental findings on NKCC stoichiometry and regulatory phosphorylation.

Main Results:

  • NKCC maintains high intracellular chloride, essential for epithelial salt transport and neural function.
  • NKCC plays a role in offsetting osmotic cell shrinkage by mediating ion influx.
  • Evidence suggests NKCC cycles are electrically silent with specific ion stoichiometries (1:1:2 or 2:1:3).
  • NKCC activity is regulated by phosphorylation/dephosphorylation and inhibited by physiological intracellular chloride levels.

Conclusions:

  • The Na(+)-K(+)-Cl(-) cotransporter (NKCC) is a critical ion transporter with diverse cellular roles.
  • Further research is needed to fully elucidate NKCC's function in cell volume regulation and the cell cycle.
  • Understanding NKCC regulation, particularly its inhibition by intracellular chloride, is key to comprehending its overall physiological significance.

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