Molecular determinants of membrane potential dependence in vertebrate gap junction channels

Ana Revilla, Michael V.L. Bennett, Luis C. Barrio

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30 Scopus citations


The conductance, gj, of many gap junctions depends on voltage between the coupled cells (transjunctional voltage, Vj) with little effect of the absolute membrane potential (Vm) in the two cells; others show combined Vj, and Vm dependence. We examined the molecular determinants of Vm dependence by using rat connexin 43 expressed in paired Xenopus oocytes. These junctions have, in addition to Vj dependence, Vm dependence such that equal depolarization of both cells decreases gj. The dependence of gj on Vm was abolished by truncation of the C-terminal domain (CT) at residue 242 but not at 257. There are two charged residues between 242 and 257. In full-length Cx43, mutations neutralizing either one of these charges, Arg243Gln and Asp245Gln, decreased and increased Vm dependence, respectively, suggesting that these residues are part of the Vm sensor. Mutating both residues together abolished Vm dependence, although there is no net change in charge. The neutralizing mutations, together or separately, had no effect on Vj dependence. Thus, the voltage sensors must differ. However, Vj gating was somewhat modulated by Vm, and Vm gating was reduced when the Vj gate was closed. These data suggest that the two forms of voltage dependence are mediated by separate but interacting domains.

Original languageEnglish (US)
Pages (from-to)14760-14765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Dec 19 2000

ASJC Scopus subject areas

  • General


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