TY - JOUR
T1 - Modulation of metabolic communication through gap junction channels by transjunctional voltage; Synergistic and antagonistic effects of gating and ionophoresis
AU - Palacios-Prado, Nicolás
AU - Bukauskas, Feliksas F.
N1 - Funding Information:
Dr. Michael V.L. Bennett for helpful comments and remarks, and Angele Bukauskiene for excellent technical assistance. This work was supported by NIH Grants, R01NS072238 and RO1HL084464 to F.F.B.
PY - 2012/8
Y1 - 2012/8
N2 - Gap junction (GJ) channels assembled from connexin (Cx) proteins provide a structural basis for direct electrical and metabolic cell-cell communication. Here, we focus on gating and permeability properties of Cx43/Cx45 heterotypic GJs exhibiting asymmetries of both voltage-gating and transjunctional flux (Jj) of fluorescent dyes depending on transjunctional voltage (V j). Relatively small differences in the resting potential of communicating cells can substantially reduce or enhance this flux at relative negativity or positivity on Cx45 side, respectively. Similarly, series of V j pulses resembling bursts of action potentials (APs) reduce J j when APs initiate in the cell expressing Cx43 and increase J j when APs initiate in the cell expressing Cx45. Jj of charged fluorescent dyes is affected by ionophoresis and Vj-gating and the asymmetry of Jj-Vj dependence in heterotypic GJs is enhanced or reduced when ionophoresis and Vj-gating work in a synergistic or antagonistic manner, respectively. Modulation of cell-to-cell transfer of metabolites and signaling molecules by Vj may occur in excitable as well as non-excitable tissues and may be more expressed in the border between normal and pathological regions where intercellular gradients of membrane potential and concentration of ions are substantially altered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
AB - Gap junction (GJ) channels assembled from connexin (Cx) proteins provide a structural basis for direct electrical and metabolic cell-cell communication. Here, we focus on gating and permeability properties of Cx43/Cx45 heterotypic GJs exhibiting asymmetries of both voltage-gating and transjunctional flux (Jj) of fluorescent dyes depending on transjunctional voltage (V j). Relatively small differences in the resting potential of communicating cells can substantially reduce or enhance this flux at relative negativity or positivity on Cx45 side, respectively. Similarly, series of V j pulses resembling bursts of action potentials (APs) reduce J j when APs initiate in the cell expressing Cx43 and increase J j when APs initiate in the cell expressing Cx45. Jj of charged fluorescent dyes is affected by ionophoresis and Vj-gating and the asymmetry of Jj-Vj dependence in heterotypic GJs is enhanced or reduced when ionophoresis and Vj-gating work in a synergistic or antagonistic manner, respectively. Modulation of cell-to-cell transfer of metabolites and signaling molecules by Vj may occur in excitable as well as non-excitable tissues and may be more expressed in the border between normal and pathological regions where intercellular gradients of membrane potential and concentration of ions are substantially altered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
KW - Connexin
KW - Dye transfer
KW - Heterotypic channel
KW - Signaling asymmetry
KW - Transjunctional permeability and flux
KW - Voltage gating
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U2 - 10.1016/j.bbamem.2011.09.001
DO - 10.1016/j.bbamem.2011.09.001
M3 - Review article
C2 - 21930112
AN - SCOPUS:84861638257
SN - 0005-2736
VL - 1818
SP - 1884
EP - 1894
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 8
ER -