Apr 18, 2020

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

BioRxiv : the Preprint Server for Biology
J. van de WeilNicholas Dale

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 (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DN in glial cells of a circumscribed region of the medulla - the caudal parapyramidal area - reduced the adaptive change in tidal volume and minute ventilation by approximately 30%. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally links 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.

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Mentioned in this Paper

Patterns
CFC1 gene
Acclimatization
Elaps corallinus, homeopathic preparations
Predator
Micrurus
Contrast Used
Adaptation
Description
CFC1 wt Allele

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