{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:58:15Z","timestamp":1791917895756,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2018,9,15]],"date-time":"2018-09-15T00:00:00Z","timestamp":1536969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["GO 766\/5\u20104"],"award-info":[{"award-number":["GO 766\/5\u20104"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u201069088"],"award-info":[{"award-number":["MOP\u201069088"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions","doi-asserted-by":"publisher","award":["AIHS award"],"award-info":[{"award-number":["AIHS award"]}],"id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201606370067"],"award-info":[{"award-number":["201606370067"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GO 766\/12\u20101"],"award-info":[{"award-number":["GO 766\/12\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"Key points<\/jats:title>\nIn arterial smooth muscle, Ca2+<\/jats:sup> sparks are elementary Ca2+<\/jats:sup>\u2010release events generated by ryanodine receptors (RyRs) to cause vasodilatation by opening maxi Ca2+<\/jats:sup>\u2010sensitive K+<\/jats:sup> (BKCa<\/jats:sub>) channels.<\/jats:p><\/jats:list-item>\nThis study elucidated the contribution of T\u2010type Cav<\/jats:sub>3.2 channels in caveolae and their functional interaction with L\u2010type Cav<\/jats:sub>1.2 channels to trigger Ca2+<\/jats:sup> sparks in vascular smooth muscle cells (VSMCs).<\/jats:p><\/jats:list-item>\nOur data demonstrate that L\u2010type Cav<\/jats:sub>1.2 channels provide the predominant Ca2+<\/jats:sup> pathway for the generation of Ca2+<\/jats:sup> sparks in murine arterial VSMCs.<\/jats:p><\/jats:list-item>\nT\u2010type Cav<\/jats:sub>3.2 channels represent an additional source for generation of VSMC Ca2+<\/jats:sup> sparks. They are located in pit structures of caveolae to provide locally restricted, tight coupling between T\u2010type Cav<\/jats:sub>3.2 channels and RyRs to ignite Ca2+<\/jats:sup> sparks.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>Abstract<\/jats:title>Recent data suggest that T\u2010type Cav<\/jats:sub>3.2 channels in arterial vascular smooth muscle cells (VSMCs) and pits structure of caveolae could contribute to elementary Ca2+<\/jats:sup> signalling (Ca2+<\/jats:sup> sparks) via ryanodine receptors (RyRs) to cause vasodilatation. While plausible, their precise involvement in igniting Ca2+<\/jats:sup> sparks remains largely unexplored. The goal of this study was to elucidate the contribution of caveolar Cav<\/jats:sub>3.2 channels and their functional interaction with Cav<\/jats:sub>1.2 channels to trigger Ca2+<\/jats:sup> sparks in VSMCs from mesenteric, tibial and cerebral arteries. We used tamoxifen\u2010inducible smooth muscle\u2010specific Cav<\/jats:sub>1.2\u2212\/\u2212<\/jats:sup> (SMAKO) mice and laser scanning confocal microscopy to assess Ca2+<\/jats:sup> spark generation in VSMCs. Ni2+<\/jats:sup>, Cd2+<\/jats:sup> and methyl\u2010\u03b2\u2010cyclodextrin were used to inhibit Cav<\/jats:sub>3.2 channels, Cav<\/jats:sub>1.2 channels and caveolae, respectively. Ni2+<\/jats:sup> (50\u00a0\u03bcmol\u00a0L\u22121<\/jats:sup>) and methyl\u2010\u03b2\u2010cyclodextrin (10\u00a0mmol\u00a0L\u22121<\/jats:sup>) decreased Ca2+<\/jats:sup> spark frequency by \u223c20\u201330% in mesenteric VSMCs in a non\u2010additive manner, but failed to inhibit Ca2+<\/jats:sup> sparks in tibial and cerebral artery VSMCs. Cd2+<\/jats:sup> (200\u00a0\u03bcmol\u00a0L\u22121<\/jats:sup>) suppressed Ca2+<\/jats:sup> sparks in mesenteric arteries by \u223c70\u201380%. A similar suppression of Ca2+<\/jats:sup> sparks was seen in mesenteric artery VSMCs of SMAKO mice. The remaining Ca2+<\/jats:sup> sparks were fully abolished by Ni2+<\/jats:sup> or methyl\u2010\u03b2\u2010cyclodextrin. Our data demonstrate that Ca2+<\/jats:sup> influx through CaV<\/jats:sub>1.2 channels is the primary means of triggering Ca2+<\/jats:sup> sparks in murine arterial VSMCs. CaV<\/jats:sub>3.2 channels, localized to caveolae and tightly coupled to RyR, provide an additional Ca2+<\/jats:sup> source for Ca2+<\/jats:sup> spark generation in mesenteric, but not tibial and cerebral, arteries.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276923","type":"journal-article","created":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T06:38:33Z","timestamp":1535438313000},"page":"4863-4877","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Differential targeting and signalling of voltage\u2010gated T\u2010type Cav<\/sub>3.2 and L\u2010type Cav<\/sub>1.2 channels to ryanodine receptors in mesenteric arteries"],"prefix":"10.1113","volume":"596","author":[{"given":"Gang","family":"Fan","sequence":"first","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Experimental and Clinical Research Center (ECRC) Campus Buch Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Ka\u00dfmann","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Experimental and Clinical Research Center (ECRC) Campus Buch Berlin Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Hashad","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Hotchkiss Brain and Libin Cardiovascular Institutes University of Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5174-186X","authenticated-orcid":false,"given":"Donald G.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University London ON 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