Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO2.
CO2readily combines with H2O to form [Formula: see text] and H+Because an increase of only 100 nM in the concentration of H+(a decrease of 0.1 unit of pH) in blood can prove fatal, the regulated excretion of CO2during breathing is an essential life-preserving process. In rodents and humans, this vital process is mediated in part via the direct sensing of CO2via connexin26 (Cx26). CO2binds to hemichannels of Cx26 causing them to open and allow release of the neurotransmitter ATP. If Cx26 were to be a universal and important CO2sensor across all homeothermic animals, then a simple hypothesis would posit that it should exhibit evolutionary adaptation in animals with different homeostatic set points for the regulation of partial pressure of arterial CO2(PaCO2). In humans and rats, PaCO2is regulated around a set point of 40 mmHg. By contrast, birds are able to maintain cerebral blood flow and breathing at much lower levels of PaCO2Fossorial mammals, such as the mole rat, live exclusively underground in burrows that are both hypoxic and hypercapnic and can thrive under very hypercapnic conditions. We have therefore compared the CO2sensitivity of Cx26 from human, chicken, rat and mole rat (Heterocephalus glaber). We find that both the affinity and cooperativity of CO2binding to Cx26 have been subjected to evolutionary adaption in a manner consistent with the homeostatic requirements of these four species. This is analogous to the evolutionary adaptation of haemoglobin to the needs of O2transport across the animal kingdom and supports the hypothesis that Cx26 is an important and universal CO2sensor in homeotherms.
School of Life Sciences, University of Warwick, Gibbet Hill Rd, Coventry CV4 7AL, UK.
Elizabeth
E
de Wolf
School of Life Sciences, University of Warwick, Gibbet Hill Rd, Coventry CV4 7AL, UK.
Jonathan
J
Cook
School of Life Sciences, University of Warwick, Gibbet Hill Rd, Coventry CV4 7AL, UK n.e.dale@warwick.ac.uk.
Nicholas
0000-0003-2196-2949
N
Dale
D000064:Acclimatization; D000818:Animals; D002245:Carbon Dioxide / Q000737:chemistry*; D002645:Chickens; D000072259:Connexin 26 / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans; D019577:Mole Rats; D010313:Partial Pressure; D051381:Rats; D012119:Respiration
D000072259:Connexin 26; D002245:Carbon Dioxide
breathing; chemosensitivitiy; connexin; hemichannel