{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:00:41Z","timestamp":1791352841863,"version":"4.3.1"},"reference-count":27,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p> The novel \u03b1<jats:sub>1D<\/jats:sub> Ca<jats:sup>2+<\/jats:sup> channel together with \u03b1<jats:sub>1C<\/jats:sub> Ca<jats:sup>2+<\/jats:sup> channel contribute to the L-type Ca<jats:sup>2+<\/jats:sup> current ( I<jats:sub>Ca-L<\/jats:sub>) in the mouse supraventricular tissue. However, its functional role in the heart is just emerging. We used the \u03b1<jats:sub>1D<\/jats:sub> gene knockout (KO) mouse to investigate the electrophysiological features, the relative contribution of the \u03b1<jats:sub>1D<\/jats:sub> Ca<jats:sup>2+<\/jats:sup> channel to the global I<jats:sub>Ca-L<\/jats:sub>, the intracellular Ca<jats:sup>2+<\/jats:sup> transient, the Ca<jats:sup>2+<\/jats:sup> handling by the sarcoplasmic reticulum (SR), and the inducibility of atrial fibrillation (AF). In vivo and ex vivo ECG recordings from \u03b1<jats:sub>1D<\/jats:sub> KO mice demonstrated significant sinus bradycardia, atrioventricular block, and vulnerability to AF. The wild-type mice showed no ECG abnormalities and no AF. Patch-clamp recordings from isolated \u03b1<jats:sub>1D<\/jats:sub> KO atrial myocytes revealed a significant reduction of I<jats:sub>Ca-L<\/jats:sub> (24.5%; P &lt; 0.05). However, there were no changes in other currents such as I<jats:sub>Na<\/jats:sub>, I<jats:sub>Ca-T<\/jats:sub>, I<jats:sub>K<\/jats:sub>, I<jats:sub>f<\/jats:sub>, and I<jats:sub>to<\/jats:sub> and no changes in \u03b1<jats:sub>1C<\/jats:sub> mRNA levels of \u03b1<jats:sub>1D<\/jats:sub> KO atria. Fura 2-loaded atrial myocytes showed reduced intracellular Ca<jats:sup>2+<\/jats:sup> transient (\u223c40%; P &lt; 0.05) and rapid caffeine application caused a 17% reduction of the SR Ca<jats:sup>2+<\/jats:sup> content ( P &lt; 0.05) and a 28% reduction ( P &lt; 0.05) of fractional SR Ca<jats:sup>2+<\/jats:sup> release in \u03b1<jats:sub>1D<\/jats:sub> KO atria. In conclusion, genetic deletion of \u03b1<jats:sub>1D<\/jats:sub> Ca<jats:sup>2+<\/jats:sup> channel in mice results in atrial electrocardiographic abnormalities and AF vulnerability. The electrical abnormalities in the \u03b1<jats:sub>1D<\/jats:sub> KO mice were associated with a decrease in the total I<jats:sub>Ca-L<\/jats:sub> density, a reduction in intracellular Ca<jats:sup>2+<\/jats:sup> transient, and impaired intracellular Ca<jats:sup>2+<\/jats:sup> handling. These findings provide new insights into the mechanism leading to atrial electrical dysfunction in the \u03b1<jats:sub>1D<\/jats:sub> KO mice. <\/jats:p>","DOI":"10.1152\/ajpheart.00537.2008","type":"journal-article","created":{"date-parts":[[2008,9,13]],"date-time":"2008-09-13T00:34:42Z","timestamp":1221266082000},"page":"H2017-H2024","source":"Crossref","is-referenced-by-count":52,"title":["Impaired Ca<sup>2+<\/sup> homeostasis is associated with atrial fibrillation in the \u03b1<sub>1D<\/sub> L-type Ca<sup>2+<\/sup> channel KO mouse"],"prefix":"10.1152","volume":"295","author":[{"given":"Salvatore","family":"Mancarella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuankun","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddy","family":"Karnabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxia","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"El-Sherif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Boutjdir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.10.2641"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00045-0"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.129.3.673"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1995.00430050045005"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.506857"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.80.3.345"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000121566.01778.06"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021521"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1540-8167.2001.01286.x"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14883"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101469200"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00008-X"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021792"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0417k.x"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0935295100"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-004-0940-7"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1302.001"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113310"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00013-1"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.517326"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.54.29"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.651bd.x"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.5.428"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-16-05944.2001"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.4.512"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.540070"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.80.5.720"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00537.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:13:32Z","timestamp":1567977212000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00537.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["10.1152\/ajpheart.00537.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00537.2008","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11]]}}}