Intercellular connectivity mediated by gap junctions (GJs) composed of connexin43 (Cx43) is critical to the function of excitable tissues such as the heart and brain. Disruptions to Cx43 GJ organization are thought to be a factor in cardiac arrhythmias and are also implicated in epilepsy. This article is based on a presentation to the 4th Larry and Horti Fairberg Workshop on Interactive and Integrative Cardiology and summarizes the work of Gourdie and his lab on Cx43 GJs in the heart. Background and perspective of recently published studies on the function of Cx43-interacting protein zonula occludens-(ZO)-1 in determining the organization of GJ plaques are provided. In addition how a peptide containing a PDZ-binding sequence of Cx43, developed as part of the work on cardiac GJ organization is also described, which has led to evidence for novel and unexpected roles for Cx43 in modulating healing following tissue injury.
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