Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 35, Pages 14855-14860Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0901923106
Keywords
connexin; intercellular permeability; voltage gating; dye transfer; fluorescent proteins
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Funding
- National Institutes of Health [RO1 NS036706, RO1HL084464]
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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 (V-j) Cx43/Cx45 heterotypic GJs exhibit both V-j-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 V-j pulses resembling bursts of action potentials (APs) can fully block or increase the transjunctional flux (J(j)) of dye depending on whether pulses are generated in the cell expressing Cx43 or Cx45, respectively. Asymmetry of J(j)-V-j dependence is enhanced or reduced when ionophoresis and V-j-gating act synergistically or antagonistically, whereas single channel permeability (P-gamma) remains unaffected. This modulation of intercellular signaling by V-j can play a crucial role in many aspects of intercellular communication in the adult, in embryonic development, and in tissue regeneration.
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