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. doi: 10.1073/pnas.0910059107. Epub 2010 Jan 19.
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.
任务 2 K(+) 通道在中枢神经系统中的表达出人意料地局限于少数脑干核团，包括延髓梯形核（RTN）区域。在患有导致人类先天性中枢性换气不足综合征的 Phox2b 突变的小鼠中，所有表达任务 2 的 RTN 神经元都丢失了。在 plethysmography 中，任务 2(-/-) 小鼠表现出化学感觉功能障碍，对低 CO2 浓度过度敏感，导致过度通气。任务 2 可能需要稳定化学感受细胞的膜电位。此外，任务 2(-/-) 小鼠失去了长期低氧诱导的呼吸减少，而急性颈动脉体介导的增加则得以维持。在离体延髓-脊髓标本中缺乏缺氧诱导的呼吸抑制表明表型具有中枢起源。在低氧期间产生的活性氧物质激活任务 2 可以使 RTN 神经元沉默，从而导致呼吸抑制。这些数据确定任务 2 是中枢 O2 化学感受的决定因素，并表明这种现象是由于位于延髓腹侧表面的少数神经元的活性所致。
