Breathing is essential to provide the O₂ required for metabolism and to remove its inevitable CO₂ by-product. The rate and depth of breathing is controlled to regulate the excretion of CO₂ to maintain the pH of arterial blood at physiological values. A widespread consensus is that chemosensory cells in the carotid body and brainstem measure blood and tissue pH and adjust the rate of breathing to ensure its homeostatic regulation. In this review, I shall consider the evidence that underlies this consensus and highlight historical data indicating that direct sensing of CO₂ also plays a significant role in the regulation of breathing. I shall then review work from my laboratory that provides a molecular mechanism for the direct detection of CO₂ via the gap junction protein connexin26 (Cx26) and demonstrates the contribution of this mechanism to the chemosensory regulation of breathing. As there are many pathological mutations of Cx26 in humans, I shall discuss which of these alter the CO₂ sensitivity of Cx26 and the extent to which these mutations could affect human breathing. I finish by discussing the evolution of the CO₂ sensitivity of Cx26 and its link to the evolution of amniotes.

呼吸对于提供新陈代谢所需的O ₂以及去除不可避免的CO ₂副产品至关重要。控制呼吸的速率和深度以调节CO ₂的排泄，从而将动脉血的pH维持在生理值。一个广泛的共识是，颈动脉体和脑干中的化学感应细胞测量血液和组织的 pH 值并调整呼吸速率以确保其稳态调节。在这篇综述中，我将考虑这一共识背后的证据，并重点介绍表明直接感知 CO ₂也在呼吸调节中发挥重要作用的历史数据。然后，我将回顾我的实验室的工作，该工作提供了通过间隙连接蛋白 connexin26 (Cx26) 直接检测 CO ₂的分子机制，并证明了该机制对呼吸化学感应调节的贡献。由于人类中存在许多Cx26 病理突变，我将讨论其中哪些突变改变了Cx26 的CO ₂敏感性以及这些突变对人类呼吸的影响程度。最后，我讨论了 Cx26 CO ₂敏感性的进化及其与羊膜动物进化的联系。