TASK-2 K₂p K⁺ Channel: Thoughts About Gating and Its Fitness to Physiological Function

Pflugers Arch. 2015 May;467(5):1043-53. doi: 10.1007/s00424-014-1627-7. Epub 2014 Oct 15.


TASK-2 (K2P5) was one of the earliest members of the K2P two-pore, four transmembrane domain K(+) channels to be identified. TASK-2 gating is controlled by changes in both extra- and intracellular pH through separate sensors: arginine 224 and lysine 245, located at the extra- and intracellular ends of transmembrane domain 4. TASK-2 is inhibited by a direct effect of CO2 and is regulated by and interacts with G protein subunits. TASK-2 takes part in regulatory adjustments and is a mediator in the chemoreception process in neurons of the retrotrapezoid nucleus where its pHi sensitivity could be important in regulating excitability and therefore signalling of the O2/CO2 status. Extracellular pH increases brought about by HCO3 (-) efflux from proximal tubule epithelial cells have been proposed to couple to TASK-2 activation to maintain electrochemical gradients favourable to HCO3 (-) reabsorption. We demonstrate that, as suspected previously, TASK-2 is expressed at the basolateral membrane of the same proximal tubule cells that express apical membrane Na(+)-H(+)-exchanger NHE-3 and basolateral membrane Na(+)-HCO3 (-) cotransporter NBCe1-A, the main components of the HCO3 (-) transport machinery. We also discuss critically the mechanism by which TASK-2 is modulated and impacts the process of HCO3 (-) reclaim by the proximal tubule epithelium, concluding that more than a mere shift in extracellular pH is probably involved.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bicarbonates / metabolism
  • Cell Membrane / metabolism*
  • Humans
  • Hydrogen-Ion Concentration*
  • Ion Channel Gating / physiology*
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / pathology
  • Potassium Channels, Tandem Pore Domain / metabolism*


  • Bicarbonates
  • Potassium Channels, Tandem Pore Domain