CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits

• DOI: 10.7554/elife.01213
• Publication Date: 2013-11-12T16:18:14Z
• Authors: Louise Meigh; Sophie A Greenhalgh; Thomas L Rodgers; Martin J Cann; David I Roper; Nicholas Dale
• Keywords: Random hexamer

Homeostatic regulation of the partial pressure CO2 (PCO2) is vital for life. Sensing pH has been proposed as a sufficient proxy determination PCO2 and direct CO2-sensing largely discounted. Here we show that connexin 26 (Cx26) hemichannels, causally linked to respiratory chemosensitivity, are directly modulated by CO2. A 'carbamylation motif', present in CO2-sensitive connexins (Cx26, Cx30, Cx32) but absent from CO2-insensitive (Cx31), comprises Lys125 four further amino acids orient towards Arg104 adjacent subunit hexamer. Introducing carbamylation motif into Cx31 created mutant hemichannel (mCx31) was opened increases PCO2. Mutation Cx26 mCx31 destroyed sensitivity. Course-grained computational modelling demonstrated carbamate bridge between biases open state. Carbamylation introduces new transduction principle physiological sensing DOI: http://dx.doi.org/10.7554/eLife.01213.001.