The role of pH-sensitive TASK channels in central respiratory chemoreception

  • Douglas A. Bayliss
  • Jacques Barhanin
  • Christian Gestreau
  • Patrice G. Guyenet
Invited Review

Abstract

A number of the subunits within the family of K2P background K+ channels are sensitive to changes in extracellular pH in the physiological range, making them likely candidates to mediate various pH-dependent processes. Based on expression patterns within several brainstem neuronal cell groups that are believed to function in CO2/H+ regulation of breathing, three TASK subunits—TASK-1, TASK-2, and TASK-3—were specifically hypothesized to contribute to this central respiratory chemoreflex. For the acid-sensitive TASK-1 and TASK-3 channels, despite widespread expression at multiple levels within the brainstem respiratory control system (including presumptive chemoreceptor populations), experiments in knockout mice provided no evidence for their involvement in CO2 regulation of breathing. By contrast, the alkaline-activated TASK-2 channel has a more restricted brainstem distribution and was localized to the Phox2b-expressing chemoreceptor neurons of the retrotrapezoid nucleus (RTN). Remarkably, in a Phox2b27Ala/+ mouse genetic model of congenital central hypoventilation syndrome (CCHS) that is characterized by reduced central respiratory chemosensitivity, selective ablation of Phox2b-expressing RTN neurons was accompanied by a corresponding loss of TASK-2 expression. Furthermore, genetic deletion of TASK-2 blunted RTN neuronal pH sensitivity in vitro, reduced alkaline-induced respiratory network inhibition in situ and diminished the ventilatory response to CO2/H+ in vivo. Notably, a subpopulation of RTN neurons from TASK-2−/− mice retained their pH sensitivity, at least in part due to a residual pH-sensitive background K+ current, suggesting that other mechanisms (and perhaps other K2P channels) for RTN neuronal pH sensitivity are yet to be identified.

Keywords

TASK subunits Potassium selective channels pH sensitivity Respiratory chmosensitivity 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Douglas A. Bayliss
    • 1
  • Jacques Barhanin
    • 2
    • 3
  • Christian Gestreau
    • 4
  • Patrice G. Guyenet
    • 1
  1. 1.Department of PharmacologyUniversity of Virginia School of MedicineCharlottesvilleUSA
  2. 2.LP2M-CNRS-UNS UMR 7370, Faculté de MédecineUniversité de Nice-Sophia AntipolisNice Cedex 2France
  3. 3.Laboratories of Excellence, Ion Channel Science and TherapeuticsNiceFrance
  4. 4.Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille–Unité Mixte de Recherche (UMR) 7286MarseilleFrance

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