Referenced in: none

Automatically associated channels: SK2

Title: Task2 potassium channels set central respiratory CO2 and O2 sensitivity.

Authors: Christian Gestreau, Dirk Heitzmann, Joerg Thomas, Véronique Dubreuil, Sascha Bandulik, Markus Reichold, Saïd Bendahhou, Patricia Pierson, Christina Sterner, Julie Peyronnet-Roux, Chérif Benfriha, Ines Tegtmeier, Hannah Ehnes, Michael Georgieff, Florian Lesage, Jean-François Brunet, Christo Goridis, Richard Warth, Jacques Barhanin

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2010 Feb 2 , 107, 2325-30

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20133877

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.