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In addition to the ubiquitously expressed cardiac voltage-gated L-type Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel isoform, pacemaker cells within the SAN and the atrioventricular node co-express voltage-gated L-type Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.3 and T-type Ca\n                    <jats:sub>v<\/jats:sub>\n                    3.1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels (SAN-VGCCs). The role of SAN-VGCCs in automaticity is incompletely understood. We used knockout mice carrying individual genetic ablation of Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.3 (\n                    <jats:italic>Ca<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>v<\/jats:italic>\n                    <\/jats:sub>\n                    <jats:italic>1.3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    ) or Ca\n                    <jats:sub>v<\/jats:sub>\n                    3.1 (\n                    <jats:italic>Ca<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>v<\/jats:italic>\n                    <\/jats:sub>\n                    <jats:italic>3.1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    ) channels and double mutant\n                    <jats:italic>Ca<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>v<\/jats:italic>\n                    <\/jats:sub>\n                    <jats:italic>1.3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    \/\n                    <jats:italic>Ca<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>v<\/jats:italic>\n                    <\/jats:sub>\n                    <jats:italic>3.1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/<\/jats:italic>\n                      \u2212\n                    <\/jats:sup>\n                    mice expressing only Ca\n                    <jats:sub>v<\/jats:sub>\n                    1.2 channels. We show that concomitant loss of SAN-VGCCs prevents physiological SAN automaticity, blocks impulse conduction and compromises ventricular rhythmicity. Coexpression of SAN-VGCCs is necessary for impulse formation in the central SAN. In mice lacking SAN-VGCCs, residual pacemaker activity is predominantly generated in peripheral nodal and extranodal sites by f-channels and TTX-sensitive Na\n                    <jats:sup>+<\/jats:sup>\n                    channels. In beating SAN cells, ablation of SAN-VGCCs disrupted late diastolic local intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release, which demonstrates an important role for these channels in supporting the sarcoplasmic reticulum based \u201c\n                    <jats:italic>Ca<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                      +\n                    <\/jats:sup>\n                    <jats:italic>clock<\/jats:italic>\n                    \u201d mechanism during normal pacemaking. These data implicate an underappreciated role for co-expression of SAN-VGCCs in heart automaticity and define an integral role for these channels in mechanisms that control the heartbeat.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-76049-7","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T06:02:41Z","timestamp":1604383361000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Concomitant genetic ablation of L-type Cav1.3 (\u03b11D) and T-type Cav3.1 (\u03b11G) Ca2+ channels disrupts heart automaticity"],"prefix":"10.1038","volume":"10","author":[{"given":"Matthias","family":"Baudot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Bidaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Louradour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo G.","family":"Torrente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Fossier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u00efla","family":"Talssi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00ebl","family":"Nargeot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Barr\u00e8re-Lemaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mesirca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo E.","family":"Mangoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"76049_CR1","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1152\/physrev.00018.2007","volume":"88","author":"ME Mangoni","year":"2008","unstructured":"Mangoni, M. 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