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Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness

  • Viviana Dalamon
  • Mariana C. Fiori
  • Vania A. Figueroa
  • Carolina A. Oliva
  • Rodrigo del Rio
  • Wendy Gonzalez
  • Jonathan Canan
  • Ana B. Elgoyhen
  • Guillermo A. Altenberg
  • Mauricio A. RetamalEmail author
Molecular and cellular mechanisms of disease

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 Ca2+ 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.

Keywords

Deafness Hemichannels Connexins Gap-junction channels Ion channel Mutation 

Notes

Acknowledgments

This work was supported by the Fondecyt [1120214] and Anillo [ACT 1104] to M.A.R., National Institutes of Health grants [R01 GM79629, 3R01 GM079629-03S1], and American Heart Association, Texas Affiliate Inc. Grant-in-Aid [14GRNT18750014] to G.A.A.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Viviana Dalamon
    • 1
  • Mariana C. Fiori
    • 2
  • Vania A. Figueroa
    • 3
  • Carolina A. Oliva
    • 3
  • Rodrigo del Rio
    • 4
  • Wendy Gonzalez
    • 5
  • Jonathan Canan
    • 5
  • Ana B. Elgoyhen
    • 1
    • 6
  • Guillermo A. Altenberg
    • 2
  • Mauricio A. Retamal
    • 2
    • 3
    Email author
  1. 1.Instituto de Investigaciones en Ingeniería Genética y Biología MolecularDr. Héctor N. Torres, Consejo Nacional de Investigaciones Científicas y TécnicasCiudad Autónoma de Buenos AiresArgentina
  2. 2.Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein ResearchTexas Tech University Health Sciences CenterLubbockUSA
  3. 3.Centro de Fisiología Celular e Integrativa, Facultad de MedicinaClínica Alemana Universidad del DesarrolloSantiagoChile
  4. 4.Centro de Investigación BiomédicaUniversidad Autónoma de ChileSantiagoChile
  5. 5.Centro de Bioinformática y Simulación Molecular (CBSM)Universidad de TalcaTalcaChile
  6. 6.Departamento de Farmacología, Facultad de MedicinaUniversidad de Buenos AiresCiudad Autónoma de Buenos AiresArgentina

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