Honghong Chen, Donglin Bai. 2024: The rectification of heterotypic Cx46/Cx50 gap junction channels depends on intracellular magnesium. Biophysics Reports, 10(5): 336-348. DOI: 10.52601/bpr.2024.240015
Citation: Honghong Chen, Donglin Bai. 2024: The rectification of heterotypic Cx46/Cx50 gap junction channels depends on intracellular magnesium. Biophysics Reports, 10(5): 336-348. DOI: 10.52601/bpr.2024.240015

The rectification of heterotypic Cx46/Cx50 gap junction channels depends on intracellular magnesium

  • Gap junction (GJ) intercellular communication is crucial in many physiological and pathological processes. A GJ channel is formed by head-to-head docking of two hexameric hemichannels from two neighboring cells. Heterotypic GJ channels formed by two different homomeric connexin hemichannels often display rectification properties in the current–voltage relationship while the underlying mechanisms are not fully clear. Here we studied heterotypic Cx46/Cx50 GJs at a single GJ channel level. Our data showed unitary Cx46/Cx50 GJ channel conductance (γj) rectification when 5 mmol/L Mg2+ was included in the patch pipette solution, while no γj rectification was observed when no Mg2+ was added. Including 5 mmol/L Mg2+ in pipette solution significantly decreased the γj of homotypic Cx46 GJ with little change in homotypic Cx50 γj. A missense point variant in Cx46 (E43F) reduced the Mg2+-dependent reduction in γj of Cx46 E43F GJ, indicating that E43 might be partially responsible for Mg2+-dependent decrease in γj of Cx46. A comprehensive understanding of Mg2+ modulation of GJ at the individual channel level is useful in understanding factors in modulating GJ-mediated intercellular communication in health and diseases.
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