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We hypothesize that this mechanism of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Ca\n                    <jats:sub>v<\/jats:sub>\n                    3.2 channel inhibition by Ni\n                    <jats:sup>2+<\/jats:sup>\n                    (50\u00a0\u00b5M) and caveolae disruption by methyl\u2010\u00df\u2010cyclodextrin or genetic abolition of Eps15 homology domain\u2010containing protein (EHD2) inhibited Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks in cells from young (4\u00a0months) but not old (12\u00a0months) mice. In accordance, expression of Ca\n                    <jats:sub>v<\/jats:sub>\n                    3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, caffeine (RyR activator) and thapsigargin (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transport ATPase inhibitor), we found that sufficient SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    load is a prerequisite for the Ca\n                    <jats:sub>V<\/jats:sub>\n                    3.2\u2010RyR axis to generate Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks. We identified a fraction of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd\n                    <jats:sup>3+<\/jats:sup>\n                    (100\u00a0\u00b5M), but insensitive to Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 and Ca\n                    <jats:sub>V<\/jats:sub>\n                    3.2 channel blockade. Our data demonstrate that the VSMC Ca\n                    <jats:sub>V<\/jats:sub>\n                    3.2\u2010RyR axis is down\u2010regulated by aging. This defective Ca\n                    <jats:sub>V<\/jats:sub>\n                    3.2\u2010RyR coupling is counterbalanced by a Gd\n                    <jats:sup>3+<\/jats:sup>\n                    sensitive Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pathway providing compensatory Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx for triggering Ca\n                    <jats:sup>2+<\/jats:sup>\n                    sparks in aged VSMCs.\n                  <\/jats:p>","DOI":"10.1111\/acel.13134","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T17:41:14Z","timestamp":1584553274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Age attenuates the T\u2010type Ca\n                    <sub>V<\/sub>\n                    3.2\u2010RyR axis in vascular smooth muscle"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1894-3253","authenticated-orcid":false,"given":"Gang","family":"Fan","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC) a joint cooperation between the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine (MDC) Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Hunan Cancer Hospital The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Ka\u00dfmann","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC) a joint cooperation between the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine (MDC) Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqiu","family":"Cui","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC) a joint cooperation between the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine (MDC) Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Matthaeus","sequence":"additional","affiliation":[{"name":"Crystallography Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Kunz","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility Max Delbr\u00fcck Center for Molecular Medicine (MDC) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC) a joint cooperation between the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine (MDC) Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hunan Cancer Hospital The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xie","sequence":"additional","affiliation":[{"name":"Hunan Cancer Hospital The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha 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