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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/C966    most recent 00008.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mese, G. Articles by White, T. W. Search for Related Content PubMed PubMed Citation Articles by Mese, G. Articles by White, T. W.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Connexin26 deafness associated mutations show altered permeability to large cationic molecules

Gülistan Mee,¹ Virginijus Valiunas,² Peter R. Brink,² and Thomas W. White²

¹Graduate Program in Genetics and the ²Department of Physiology and Biophysics, State University of New York, Stony Brook, New York

Submitted 8 January 2008 ; accepted in final form 4 August 2008

Intercellular communication is important for cochlear homeostasis because connexin26 (Cx26) mutations are the leading cause of hereditary deafness. Gap junctions formed by different connexins have unique selectivity to large molecules, so compensating for the loss of one isoform can be challenging in the case of disease causing mutations. We compared the properties of Cx26 mutants T8M and N206S with wild-type channels in transfected cells using dual whole cell voltage clamp and dye flux experiments. Wild-type and mutant channels demonstrated comparable ionic coupling, and their average unitary conductance was 106 and 60 pS in 120 mM K⁺-aspartate^– and TEA⁺-aspartate^– solution, respectively, documenting their equivalent permeability to K⁺ and TEA⁺. Comparison of cAMP, Lucifer Yellow (LY), and ethidium bromide (EtBr) transfer revealed differences in selectivity for larger anionic and cationic tracers. cAMP and LY permeability to wild-type and mutant channels was similar, whereas the transfer of EtBr through mutant channels was greatly reduced compared with wild-type junctions. Altered permeability of Cx26 to large cationic molecules suggests an essential role for biochemical coupling in cochlear homeostasis.

channel; selectivity; cochlear homeostasis; ethidium bromide; Lucifer yellow