Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity

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.
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Christian Gestreau, Dirk Heitzmann, Joerg Thomas, V. Dubreuil, Sascha Bandulik, et al.. Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2010, 107 (5), pp.2325-2330. ⟨10.1073/pnas.0910059107⟩. ⟨hal-01229488⟩

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