Heterotypic gap junction channels as voltage-sensitive valves for intercellular signaling

Nicolas Palacios-Prado, Feliksas F. Bukauskas

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Gap junction (GJ) channels assembled from connexin (Cx) proteins provide a structural basis for direct electrical and metabolic cell-cell communication. By combining fluorescence imaging and dual whole-cell voltage clamp methods, we demonstrate that in response to transjunctional voltage (Vj) Cx43/Cx45 heterotypic GJs exhibit both Vj-gating and dye transfer asymmetries. The later is affected by ionophoresis of charged fluorescent dyes and voltage-dependent gating. We demonstrate that small differences in resting (holding) potentials of communicating cells can fully block (at relative negativity on Cx45 side) or enhance (at relative positivity on Cx45 side) dye transfer. Similarly, series of high frequency Vj pulses resembling bursts of action potentials (APs) can fully block or increase the transjunctional flux (Jj) of dye depending on whether pulses are generated in the cell expressing Cx43 or Cx45, respectively. Asymmetry of J j-Vj dependence is enhanced or reduced when ionophoresis and Vj-gating act synergistically or antagonistically, whereas single channel permeability (Pγ) remains unaffected. This modulation of intercellular signaling by Vj can play a crucial role in many aspects of intercellular communication in the adult, in embryonic development, and in tissue regeneration.

Original languageEnglish (US)
Pages (from-to)14855-14860
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
StatePublished - Sep 1 2009
Externally publishedYes


  • Connexin
  • Dye transfer
  • Fluorescent proteins
  • Intercellular permeability
  • Voltage gating

ASJC Scopus subject areas

  • General


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