{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:20:36Z","timestamp":1788668436400,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007684","name":"Ministry of Education and Science of Ukraine","doi-asserted-by":"publisher","award":["0122U001535"],"award-info":[{"award-number":["0122U001535"]}],"id":[{"id":"10.13039\/501100007684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007684","name":"Ministry of Education and Science of Ukraine","doi-asserted-by":"publisher","award":["0122U002126"],"award-info":[{"award-number":["0122U002126"]}],"id":[{"id":"10.13039\/501100007684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007684","name":"Ministry of Education and Science of Ukraine","doi-asserted-by":"publisher","award":["BHF PG\/09\/063"],"award-info":[{"award-number":["BHF PG\/09\/063"]}],"id":[{"id":"10.13039\/501100007684","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Academy of Science of Ukraine","award":["0122U001535"],"award-info":[{"award-number":["0122U001535"]}]},{"name":"National Academy of Science of Ukraine","award":["0122U002126"],"award-info":[{"award-number":["0122U002126"]}]},{"name":"National Academy of Science of Ukraine","award":["BHF PG\/09\/063"],"award-info":[{"award-number":["BHF PG\/09\/063"]}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["0122U001535"],"award-info":[{"award-number":["0122U001535"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["0122U002126"],"award-info":[{"award-number":["0122U002126"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["BHF PG\/09\/063"],"award-info":[{"award-number":["BHF PG\/09\/063"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>TRP channels are expressed both in vascular myocytes and endothelial cells, but knowledge of their operational mechanisms in vascular tissue is particularly limited. Here, we show for the first time the biphasic contractile reaction with relaxation followed by a contraction in response to TRPV4 agonist, GSK1016790A, in a rat pulmonary artery preconstricted with phenylephrine. Similar responses were observed both with and without endothelium, and these were abolished by the TRPV4 selective blocker, HC067047, confirming the specific role of TRPV4 in vascular myocytes. Using selective blockers of BKCa and L-type voltage-gated Ca2+ channels (CaL), we found that the relaxation phase was inducted by BKCa activation generating STOCs, while subsequent slowly developing TRPV4-mediated depolarisation activated CaL, producing the second contraction phase. These results are compared to TRPM8 activation using menthol in rat tail artery. Activation of both types of TRP channels produces highly similar changes in membrane potential, namely slow depolarisation with concurrent brief hyperpolarisations due to STOCs. We thus propose a general concept of bidirectional TRP-CaL-RyR-BKCa molecular and functional signaloplex in vascular smooth muscles. Accordingly, both TRPV4 and TRPM8 channels enhance local Ca2+ signals producing STOCs via TRP\u2013RyR\u2013BKCa coupling while simultaneously globally engaging BKCa and CaL channels by altering membrane potential.<\/jats:p>","DOI":"10.3390\/biom13050759","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T04:30:47Z","timestamp":1682569847000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Bidirectional TRP\/L Type Ca2+ Channel\/RyR\/BKCa Molecular and Functional Signaloplex in Vascular Smooth Muscles"],"prefix":"10.3390","volume":"13","author":[{"given":"Dariia O.","family":"Dryn","sequence":"first","affiliation":[{"name":"O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 01024 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariia I.","family":"Melnyk","sequence":"additional","affiliation":[{"name":"O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 01024 Kyiv, Ukraine"},{"name":"ESC \u201cInstitute of Biology and Medicine\u201d, Taras Shevchenko National University of Kyiv, 01601 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donal","family":"Melanaphy","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5383-6683","authenticated-orcid":false,"given":"Igor V.","family":"Kizub","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences Education, Queen\u2019s University Belfast, Whitla Medical Building, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-149X","authenticated-orcid":false,"given":"Alexander V.","family":"Zholos","sequence":"additional","affiliation":[{"name":"ESC \u201cInstitute of Biology and Medicine\u201d, Taras Shevchenko National University of Kyiv, 01601 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1159\/000159111","article-title":"Calcium channels in vascular smooth muscle cells","volume":"32","author":"Hughes","year":"1995","journal-title":"J. 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