CO2-dependent opening of connexin 26 and related β connexins


Corresponding author N. Dale: Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.


We have previously shown connexin mediated CO2-dependent ATP release from the surface of the medulla oblongata. Given the localization of connexin 26 (Cx26) to the chemosensing areas of the medulla, we have tested in a heterologous expression system (HeLa cells) whether Cx26 may be sensitive to changes in inline image. Cx26 responded to an increase in inline image at constant extracellular pH by opening and to a decrease in inline image by closing. Furthermore, Cx26 was partially activated at a physiological inline image of around 40 mmHg. Cx26 in isolated patches responded to changes in inline image, suggesting direct CO2 sensitivity of the hemichannel to CO2. Heterologous expression of Cx26 in HeLa cells was sufficient to endow them with the capacity to release ATP in a CO2-sensitive manner. We have examined other heterologously expressed connexins for their ability to respond to changes in inline image. The closely related β connexins Cx30 and Cx32 also displayed sensitivity to changes in inline image, but with slightly different characteristics from Cx26. The more distant Cx43 exhibited CO2-dependent closing (possibly mediated through intracellular acidification), while Cx36 displayed no CO2 sensitivity. These surprising findings suggest that connexins may play a hitherto unappreciated variety of signalling roles, and that Cx26 and related β connexins may impart direct sensitivity to CO2 throughout the brain.