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

  • Molecular and cellular mechanisms of disease
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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.

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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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Authors and Affiliations

  1. 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

    Viviana Dalamon & Ana B. Elgoyhen

  2. Department of Cell Physiology and Molecular Biophysics, and Center for Membrane Protein Research, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Mariana C. Fiori, Guillermo A. Altenberg & Mauricio A. Retamal

  3. Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Avenida Las Condes, 12438, Santiago, Chile

    Vania A. Figueroa, Carolina A. Oliva & Mauricio A. Retamal

  4. Centro de Investigación Biomédica, Universidad Autónoma de Chile, Santiago, Chile

    Rodrigo del Rio

  5. Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile

    Wendy Gonzalez & Jonathan Canan

  6. Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina

    Ana B. Elgoyhen

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  1. Viviana Dalamon
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  2. Mariana C. Fiori
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Correspondence to Mauricio A. Retamal.

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Dalamon, V., Fiori, M.C., Figueroa, V.A. et al. Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness. Pflugers Arch - Eur J Physiol 468, 909–918 (2016). https://doi.org/10.1007/s00424-016-1788-7

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  • DOI: https://doi.org/10.1007/s00424-016-1788-7

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