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机构地区:[1]Department of Physiology and Pharmacology,University of Western Ontario,London,Ontario,Canada
出 处:《Biophysics Reports》2024年第5期336-348,共13页生物物理学报(英文版)
基 金:supported by Natural Sciences and Engineering Research Council of Canada(288241to D.B.)。
摘 要: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(γ_(j))rectification when 5 mmol/L Mg^(2+)was included in the patch pipette solution,while noγ_(j)rectification was observed when no Mg^(2+)was added.Including 5 mmol/L Mg^(2+)in pipette solution significantly decreased theγ_(j)of homotypic Cx46GJ with little change in homotypic Cx50γ_(j).A missense point variant in Cx46(E43F)reduced the Mg^(2+)-dependent reduction inγ_(j)of Cx46 E43F GJ,indicating that E43 might be partially responsible for Mg^(2+)-dependent decrease inγ_(j)of Cx46.A comprehensive understanding of Mg^(2+)modulation of GJ at the individual channel level is useful in understanding factors in modulating GJ-mediated intercellular communication in health and diseases.
关 键 词:Gap junction channel Heterotypic gap junction RECTIFICATION Single channel analysis Patch clamp
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