title: Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness.
abstract: Gap-junction channels (GJCs) are formed by head-to-head association of two hemichannels (HCs, connexin hexamers). HCs and GJCs are permeable to ions and hydrophilic molecules of up to Mr ~1 kDa. Hearing impairment of genetic origin is common, and mutations of connexin 26 (Cx26) are its major cause. We recently identified two novel Cx26 mutations in hearing-impaired subjects, L10P and G109V. L10P forms functional GJCs with slightly altered voltage dependence and HCs with decrease ATP/cationic dye selectivity. G109V does not form functional GJCs, but forms functional HCs with enhanced extracellular Ca(2+) sensitivity and subtle alterations in voltage dependence and ATP/cationic dye selectivity. Deafness associated with G109V could result from decreased GJCs activity, whereas deafness associated to L10P may have a more complex mechanism that involves changes in HC permeability.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Dr. Héctor N. Torres, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Dalamon
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Fiori
authors.affiliation: Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Avenida Las Condes, 12438, Santiago, Chile.
authors.forename: Vania A
authors.initials: VA
authors.lastname: Figueroa
authors.affiliation: Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Avenida Las Condes, 12438, Santiago, Chile.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Oliva
authors.affiliation: Centro de Investigación Biomédica, Universidad Autónoma de Chile, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Del Rio
authors.affiliation: Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile.
authors.forename: Wendy
authors.initials: W
authors.lastname: Gonzalez
authors.affiliation: Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Canan
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Dr. Héctor N. Torres, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires, Argentina.|Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Elgoyhen
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Altenberg
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX, USA. mretamal@udd.cl.|Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Avenida Las Condes, 12438, Santiago, Chile. mretamal@udd.cl.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Retamal
mesh_terms: D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003638:Deafness / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating; D009154:Mutation; D014981:Xenopus
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Connexins; Deafness; Gap-junction channels; Hemichannels; Ion channel; Mutation