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Small cerebral resistance arteries that run across the surface of the brain (pial arteries) showed enhanced pressure-induced constriction due to diminished activity of large-conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    (BK) channels\u2014key vasodilatory ion channels of cerebral vascular smooth muscle cells. Activation of BK channels by transient intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals from the sarcoplasmic reticulum (SR), termed Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks, leads to hyperpolarization and vasodilation. Combining patch-clamp electrophysiology, high-speed confocal imaging, and proximity ligation assays, we demonstrated that this vasodilatory mechanism is uncoupled in hypertensive mice, an effect attributable to physical separation of the plasma membrane from the SR rather than altered properties of BK channels or Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks, which remained intact. This pathogenic mechanism is responsible for the observed increase in constriction and can now be targeted as a possible avenue for restoring healthy CBF in vascular dementia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2307513120","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T15:11:27Z","timestamp":1691421087000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Uncoupling of Ca\n                    <sup>2+<\/sup>\n                    sparks from BK channels in cerebral arteries underlies hypoperfusion in hypertension-induced vascular dementia"],"prefix":"10.1073","volume":"120","author":[{"given":"Jade L.","family":"Taylor","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom"},{"name":"Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance National Health Service Foundation Trust, University of Manchester, Manchester M13 9PL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy R.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom"},{"name":"Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance National Health Service Foundation Trust, University of Manchester, Manchester M13 9PL, United Kingdom"},{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana-Emilia","family":"Mosneag","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance National Health Service Foundation Trust, University of Manchester, Manchester M13 9PL, United Kingdom"},{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thea G. 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