Connexin26 mediates CO₂-dependent regulation of breathing via glial cells of the medulla oblongata.

ABSTRACT: 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.

SUBMITTER: van de Wiel J 

PROVIDER: S-EPMC7505967 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature