De novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia

Publication date: Available online 20 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Luis A. Cea, Elisa Balboa, Aníbal A. Vargas, Carlos Puebla, María C. Brañes, Rosalba Escamilla, Tomás Regueira, Juan C. SáezAbstractEndotoxemia caused by bacterial lipopolysaccharides (LPSs) leads to severe skeletal muscular deterioration, starting with higher membrane permeability and decline in resting membrane potential (RMP). However, the molecular mechanism of such changes remains unclear. Here, we evaluated the possible involvement of connexin43- and conneixn45-based hemichannels (Cx43 and Cx45 HCs, respectively) as putative mediators of sarcolemmal dysfunctions induced by LPS in control (Cx43fl/flCx45fl/fl) and connexin43/connexin45 expression-deficient (Cx43fl/flCx45fl/fl:Myo-Cre) skeletal mice myofibers. At 5 h of endotoxemia, control myofibers presented Cx43 and Cx45 proteins forming functional HCs. Additionally, myofibers from endotoxic control mice showed dye uptake in vivo, which was inhibited by carbenoxolone, a Cx HC blocker. A similar increase in membrane permeability was observed in myofibers freshly isolated from skeletal muscle of mice treated for 5 h with LPS, which was blocked by the Cx HC blocker and was absent in myofibers from mice simultaneously treated with LPS and boldine, which is a Cx HC blocker. The increase in sarcolemmal permeability was mimicked by isolated myofibers treated with pro-inflammatory cytokines ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research