Breathing is highly sensitive to the PCO₂ of arterial blood. Although CO₂ is detected via the proxy of pH, CO₂ acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO₂-binding to Cx26 to devise a dominant negative subunit (Cx26^DN) that removes the CO₂-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26^DN in glial cells of a circumscribed region of the mouse medulla - the caudal parapyramidal area – reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO₂. As central chemosensors mediate about 70% of the total response to hypercapnia, CO₂-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO₂. Our data unequivocally link the direct sensing of CO₂ to the chemosensory control of breathing and demonstrates that CO₂-binding to Cx26 is a key transduction step in this fundamental process.

呼吸对动脉血中的 PCO ₂高度敏感。虽然 CO ₂是通过 pH 值来检测的，但通过 Cx26 直接作用的 CO ₂也可能有助于呼吸的调节。在这里，我们利用对CO ₂与Cx26 结合的结构基序的了解来设计显性负亚基(Cx26 ^DN )，其消除内源表达的野生型Cx26 的CO ₂敏感性。小鼠髓质边界区域（尾侧锥体旁区域）的胶质细胞中 Cx26 ^DN的表达使潮气量和每分钟通气量的适应性变化在 6% 吸入的 CO ₂下减少了约 30%。由于中枢化学传感器介导对高碳酸血症的总反应的约70%，因此通过尾侧锥体旁区域中的Cx26的CO ₂感应贡献了中枢介导的对CO ₂通气反应的约45%。我们的数据明确地将CO ₂的直接传感与呼吸的化学感应控制联系起来，并证明CO ₂与Cx26 的结合是这一基本过程中的关键转导步骤。