Task2 Potassium Channels Set Central Respiratory CO2 and O2 Sensitivity

Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2325-30. doi: 10.1073/pnas.0910059107. Epub 2010 Jan 19.

Abstract

Task2 K(+) channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2(-/-) mice showed disturbed chemosensory function with hypersensitivity to low CO(2) concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2(-/-) mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstem-spinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O(2) chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain Stem / pathology
  • Brain Stem / physiology
  • Brain Stem / physiopathology
  • Carbon Dioxide / physiology*
  • Chemoreceptor Cells / pathology
  • Chemoreceptor Cells / physiology
  • Disease Models, Animal
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology
  • Humans
  • Hypercapnia / physiopathology
  • Hypoxia / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Oxygen / physiology*
  • Plethysmography, Whole Body
  • Potassium Channels, Tandem Pore Domain / deficiency
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / physiology*
  • Pregnancy
  • Respiratory Center / physiology*
  • Respiratory Physiological Phenomena
  • Sleep Apnea, Central / etiology
  • Sleep Apnea, Central / genetics
  • Sleep Apnea, Central / physiopathology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology

Substances

  • Homeodomain Proteins
  • Kcnk5 protein, mouse
  • NBPhox protein
  • Potassium Channels, Tandem Pore Domain
  • Transcription Factors
  • Carbon Dioxide
  • Oxygen