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The disconnect between experimental and clinical outcomes to date may be due, in part, to the use of tools which yield information about aggregate permeability or Ca<jats:sup>2+<\/jats:sup> responses in lung or in endothelial monolayers. The teaching point of this review is to \u201cunpack the box,\u201d i.e. consider the many potential issues which could impact interpretation of outcomes. These include phenotypic heterogeneity and resultant segment\u2010specific permeability responses, methodologic issues related to permeability measures, contributions from Ca<jats:sup>2+<\/jats:sup> channels in cells other than endothelium\u2014such as alveolar macrophages or blood leukocytes), Ca<jats:sup>2+<\/jats:sup> dynamic patterns, rather than averaged Ca<jats:sup>2+<\/jats:sup> responses to channel activation, and the background context, such as changes in endothelial bioenergetics with sepsis. Any or all of these issues might color interpretation of permeability and Ca<jats:sup>2+<\/jats:sup> signaling in lung.<\/jats:p>","DOI":"10.1177\/2045893217738218","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T16:32:35Z","timestamp":1508257955000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Permeability and calcium signaling in lung endothelium: unpack the box\u2026"],"prefix":"10.1002","volume":"8","author":[{"given":"Mary I.","family":"Townsley","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of South Alabama Mobile AL 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