{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:03:22Z","timestamp":1792623802130,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH\u2010000522\u201000"],"award-info":[{"award-number":["MOH\u2010000522\u201000"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/CIRG\/1469\/2017"],"award-info":[{"award-number":["NMRC\/CIRG\/1469\/2017"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/OFIRG\/0070\/2018"],"award-info":[{"award-number":["NMRC\/OFIRG\/0070\/2018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    Calcium influx via the L\u2010type voltage\u2010gated Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 calcium channel in smooth muscle cells regulates vascular contraction. Calcium channel blockers (CCBs) are widely used to treat hypertension by inhibiting Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels. Using the vascular smooth muscle cell line, A7r5 and primary culture of cerebral vascular smooth muscle cells, we found that the expression and function of Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels are downregulated during hypoxia. Furthermore, hypoxia induces structural changes in Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels via alternative splicing. The expression of exon 9* is upregulated, whereas exon 33 is downregulated. Such structural alterations of Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels are caused by the decreased expression of RNA\u2010binding proteins RNA\u2010binding protein fox\u20101 homolog 1 and 2 (RbFox1 and RbFox2). Overexpression of RbFox1 and RbFox2 prevents hypoxia\u2010induced exon 9* inclusion and exon 33 exclusion. Importantly, such structural alterations of the Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channel partly contribute to the enhanced sensitivity of Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 to isradipine (a CCB) under hypoxia. Overexpression of RbFox1 and RbFox2 successfully reduces isradipine sensitivity in hypoxic smooth muscle cells. Our results suggest a new strategy to manage ischemic diseases such as stroke and myocardial infarction.\n                  <\/jats:p>","DOI":"10.1111\/febs.17159","type":"journal-article","created":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T02:00:04Z","timestamp":1716602404000},"page":"4265-4285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Enhanced isradipine sensitivity in vascular smooth muscle cells due to hypoxia\u2010induced Ca\n                    <sub>v<\/sub>\n                    1.2 splicing and\n                    <scp>RbFox1<\/scp>\n                    \/Fox2 downregulation"],"prefix":"10.1111","volume":"291","author":[{"given":"Charlene Priscilla","family":"Poore","sequence":"first","affiliation":[{"name":"Calcium Signaling Laboratory National Neuroscience Institute  Singapore City 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