title: Connexin26 hemichannels with a mutation that causes KID syndrome in humans lack sensitivity to CO2.
abstract: <title>Abstract</title>Mutations in connexin26 (Cx26) underlie a range of serious human pathologies. Previously we have shown that Cx26 hemichannels are directly opened by CO2 (Meigh et al., 2013). However the effects of human disease-causing mutations on the CO2 sensitivity of Cx26 are entirely unknown. Here, we report the first connection between the CO2 sensitivity of Cx26 and human pathology, by demonstrating that Cx26 hemichannels with the mutation A88V, linked to Keratitis-Ichthyosis-Deafness syndrome, are both CO2 insensitive and associated with disordered breathing in humans.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Meigh
authors.affiliation: Division of Neonatal Pediatrics, Connecticut Children's Medical Center NICU, University of Connecticut Health Center, Farmington, United States.
authors.forename: Naveed
authors.initials: N
authors.lastname: Hussain
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, United States.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Mulkey
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dale
mesh_terms: D002245:Carbon Dioxide / Q000494:pharmacology*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D007057:Ichthyosis / Q000235:genetics*; D007634:Keratitis / Q000235:genetics*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020182:Sleep Apnea, Central / Q000235:genetics
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C000607044:Gjb2 protein, rat; D050505:Mutant Proteins; D000072259:Connexin 26; D002245:Carbon Dioxide
keywords: 2; biophysics; gap junctions; hemichannels; human; human biology; medicine; rat; respiratory apnea; structural biology