Huckstepp, Robert T. R., Eason, Robert, Sachdev, Anshu and Dale, Nicholas. (2010) CO2-dependent opening of connexin 26 and related beta connexins. Journal of Physiology, Vol.588 (No.20). pp. 3921-3931. ISSN 0022-3751

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Abstract

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 P-CO2. Cx26 responded to an increase in P-CO2 at constant extracellular pH by opening and to a decrease in P-CO2 by closing. Furthermore, Cx26 was partially activated at a physiological P-CO2 of around 40 mmHg. Cx26 in isolated patches responded to changes in P-CO2, 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 P-CO2. The closely related beta connexins Cx30 and Cx32 also displayed sensitivity to changes in P-CO2, 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 beta connexins may impart direct sensitivity to CO2 throughout the brain.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Journal or Publication Title:	Journal of Physiology
Publisher:	Wiley-Blackwell Publishing Ltd.
ISSN:	0022-3751
Date:	15 October 2010
Volume:	Vol.588
Number:	No.20
Number of Pages:	11
Page Range:	pp. 3921-3931
Identification Number:	10.1113/jphysiol.2010.192096
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Medical Research Council (Great Britain) (MRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)
URI:	http://wrap.warwick.ac.uk/id/eprint/4970

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