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To co\u2010ordinate activities, communication among cells is required for tissue level responses to emerge. While a significant form of communication occurs by the propagation of signals between cells, the mechanism of propagation in the intact endothelium is unresolved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imaging in the endothelium of intact blood vessels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Multiple mechanisms maintain communication so that Ca\n                      <jats:sup>2+<\/jats:sup>\n                      wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP\n                      <jats:sub>3<\/jats:sub>\n                      \u2010induced IP\n                      <jats:sub>3<\/jats:sub>\n                      production transmits Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C\u2010dependent Ca\n                      <jats:sup>2+<\/jats:sup>\n                      waves across coupled cells. None of gap junctions, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      diffusion or the release of extracellular messengers is required to support this type of intercellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signals across the discontinuity and drives propagated vasodilation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These results show that signalling switches underlie endothelial cell\u2010to\u2010cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16366","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T03:54:35Z","timestamp":1713844475000},"page":"2810-2832","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Signalling switches maintain intercellular communication in the vascular endothelium"],"prefix":"10.1111","volume":"181","author":[{"given":"Charlotte","family":"Buckley","sequence":"first","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-382X","authenticated-orcid":false,"given":"Matthew D.","family":"Lee","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of 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