{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:29:10Z","timestamp":1773419350616,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>imaging reveals subcellular<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks and global<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>waves\/oscillations in vascular smooth muscle. It is well established that<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks can relax arteries, but we have previously reported that sparks can summate to generate<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>waves\/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks in the generation of myogenic tone in pressurized arterioles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Isolated retinal arterioles (25\u201340\u2009\u03bcm external diameter) were pressurized to 70\u2009<jats:styled-content style=\"fixed-case\">mmHg<\/jats:styled-content>, leading to active constriction.<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>signals were imaged from arteriolar smooth muscle in the same vessels using<jats:styled-content style=\"fixed-case\">Fluo4<\/jats:styled-content>and confocal laser microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Tone development was associated with an increased frequency of<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>oscillations, quantifiable as an increased cross\u2010correlation coefficient. Inhibition of<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>, resulted in arteriolar relaxation. Cyclopiazonic acid\u2010induced dilatation was associated with decreased<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks and oscillations but with a sustained rise in the mean global cytoplasmic<jats:styled-content style=\"fixed-case\">[<jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman>]<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">[<jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman>]<jats:sub>c<\/jats:sub><\/jats:styled-content>), as measured using<jats:styled-content style=\"fixed-case\">Fura2<\/jats:styled-content>and microfluorimetry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>This study provides direct evidence that<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global<jats:styled-content style=\"fixed-case\">[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub><\/jats:styled-content>, underlining the importance of frequency\u2010modulated signalling in vascular smooth muscle.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12044","type":"journal-article","created":{"date-parts":[[2012,11,5]],"date-time":"2012-11-05T13:46:29Z","timestamp":1352123189000},"page":"1675-1686","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp><scp>Ca<sup>2+<\/sup><\/scp><\/scp>sparks promote myogenic tone in retinal arterioles"],"prefix":"10.1111","volume":"168","author":[{"given":"J","family":"Kur","sequence":"first","affiliation":[{"name":"Centre for Vision and Vascular Science School of Medicine, Dentistry and Biomedical Sciences Queen's University Belfast 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