Effect of charge substitutions at residue His-142 on voltage gating of connexin43 channels

Junko Shibayama, Cristina Gutiérrez, Daniel González, Fabien Kieken, Akiko Seki, Jesus Requena Carrión, Paul L. Sorgen, Steven M. Taffet, Luis C. Barrio, Mario Delmar

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28 Scopus citations

Abstract

Previous studies indicate that the carboxyl terminal of connexin43 (Cx43CT) is involved in fast transjunctional voltage gating. Separate studies support the notion of an intramolecular association between Cx43CT and a region of the cytoplasmic loop (amino acids 119-144; referred to as "L2"). Structural analysis of L2 shows two α-helical domains, each with a histidine residue in its sequence (H126 and H142). Here, we determined the effect of H142 replacement by lysine, alanine, and glutamate on the voltage gating of Cx43 channels. Mutation H142E led to a significant reduction in the frequency of occurrence of the residual state and a prolongation of dwell open time. Macroscopically, there was a large reduction in the fast component of voltage gating. These results resembled those observed for a mutant lacking the carboxyl terminal (CT) domain. NMR experiments showed that mutation H142E significantly decreased the Cx43CT-L2 interaction and disrupted the secondary structure of L2. Overall, our data support the hypothesis that fast voltage gating involves an intramolecular particle-receptor interaction between CT and L2. Some of the structural constrains of fast voltage gating may be shared with those involved in the chemical gating of Cx43.

Original languageEnglish (US)
Pages (from-to)4054-4063
Number of pages10
JournalBiophysical journal
Volume91
Issue number11
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Biophysics

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    Shibayama, J., Gutiérrez, C., González, D., Kieken, F., Seki, A., Carrión, J. R., Sorgen, P. L., Taffet, S. M., Barrio, L. C., & Delmar, M. (2006). Effect of charge substitutions at residue His-142 on voltage gating of connexin43 channels. Biophysical journal, 91(11), 4054-4063. https://doi.org/10.1529/biophysj.106.085787