Submitted on January 8, 2008
Revised on August 4, 2008
Accepted on August 4, 2008
Connexin26 deafness associated mutations show altered permeability to large cationic molecules
Gulistan Mese, Virginijus Valiunas1, Peter Brink2, and Thomas W White3*
1 State University of New York, Stony Brook
2 SUNY at Stony Brook
3 State University of New York
* To whom correspondence should be addressed. E-mail: thomas.white{at}sunysb.edu.
Intercellular communication is important for cochlear homeostasis as 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 ~106pS and ~60 pS in 120mM 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 while the transfer of EtBr through mutant channels was greatly reduced compared to wild-type junctions. Altered permeability of Cx26 to large cationic molecules suggests an essential role for biochemical coupling in cochlear homeostasis.
