{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:39:35Z","timestamp":1791092375202,"version":"4.1.0"},"reference-count":39,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>\n                    The L-type calcium channel (LTCC) provides trigger Ca\n                    <jats:sup>2+<\/jats:sup>\n                    for sarcoplasmic reticulum Ca-release, and LTCC function is influenced by interacting proteins including the LTCC distal COOH terminus (DCT) and calmodulin. DCT is proteolytically cleaved and reassociates with the LTCC complex to regulate calcium channel function. DCT reduces LTCC barium current ( I\n                    <jats:sub>Ba,L<\/jats:sub>\n                    ) in reconstituted channel complexes, yet the contribution of DCT to LTCC Ca\n                    <jats:sup>2+<\/jats:sup>\n                    current ( I\n                    <jats:sub>Ca,L<\/jats:sub>\n                    ) in cardiomyocyte systems is unexplored. This study tests the hypothesis that DCT attenuates cardiomyocyte I\n                    <jats:sub>Ca,L<\/jats:sub>\n                    . We measured LTCC current and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients with DCT coexpressed in murine cardiomyocytes. We also heterologously coexpressed DCT and Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 constructs with truncations corresponding to the predicted proteolytic cleavage site, Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2\u03941801, and a shorter deletion corresponding to well-studied construct, Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2\u03941733. DCT inhibited I\n                    <jats:sub>Ba,L<\/jats:sub>\n                    in cardiomyocytes, and in human embryonic kidney (HEK) 293 cells expressing Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2\u03941801 and Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2\u03941733. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -CaM relieved DCT block in cardiomyocytes and HEK cells. The selective block of I\n                    <jats:sub>Ba,L<\/jats:sub>\n                    combined with Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -CaM effects suggested that DCT-mediated blockade may be relieved under conditions of elevated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . We therefore tested the hypothesis that DCT block is dynamic, increasing under relatively low Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and show that DCT reduced diastolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    at low stimulation frequencies but spared high frequency Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry. DCT reduction of diastolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and relief of block at high pacing frequencies and under conditions of supraphysiological bath Ca\n                    <jats:sup>2+<\/jats:sup>\n                    suggests that a physiological function of DCT is to increase the dynamic range of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients in response to elevated pacing frequencies. Our data motivate the new hypothesis that DCT is a native reverse use-dependent inhibitor of LTCC current.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00396.2012","type":"journal-article","created":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T20:45:02Z","timestamp":1354394702000},"page":"H455-H464","source":"Crossref","is-referenced-by-count":20,"title":["The cardiac L-type calcium channel distal carboxy terminus autoinhibition is regulated by calcium"],"prefix":"10.1152","volume":"304","author":[{"given":"Shawn M.","family":"Crump","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Andres","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky College of Medicine, Lexington, 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