• 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-Francois Brunet, Christo Goridis, Richard Warth, and Jacques Barhanin.
• Department of Neurovegetative Physiology, Centre National de la Recherche Scientifique, Université Paul Cézanne, 13397 Marseille, France.
• Proc. Natl. Acad. Sci. U.S.A. 2010 Feb 2;107(5):2325-30.

AbstractTask2 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.

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