{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:27:15Z","timestamp":1791188835616,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,6,14]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Congenital heart block (CHB) is an autoimmune disease that affects fetuses\/infants born to mothers with anti-Ro\/La antibodies (positive IgG). Although the hallmark of CHB is complete atrioventricular block, sinus bradycardia has been reported recently in animal models of CHB. Interestingly, knockout of the neuroendocrine \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca channel in mice results in significant sinus bradycardia and atrioventricular block, a phenotype reminiscent to that seen in CHB. Here, we tested the hypothesis that the \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca channel is a novel target for positive IgG.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Reverse transcription\u2013polymerase chain reaction, confocal indirect immunostaining, and Western blot data established the expression of the \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca channel in the human fetal heart. The effect of positive IgG on \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca current (\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            ) was characterized in heterologous expression systems (tsA201 cells and Xenopus oocytes) because of the unavailability of \u03b1\n            <jats:sub>1D<\/jats:sub>\n            -specific modulators. \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            activated at negative potentials (between \u221260 and \u221250 mV). Positive IgG inhibited \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            in both expression systems. This inhibition was rescued by a Ca channel activator, Bay K8644. No effect on \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            was observed with negative IgG and denatured positive IgG. Western blot data showed that positive IgG binds directly to \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca channel protein.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            The data are the first to demonstrate (1) expression of the \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca channel in human fetal heart, (2) inhibition of \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            by positive IgG, and (3) direct cross-reactivity of positive IgG with the \u03b1\n            <jats:sub>1D<\/jats:sub>\n            Ca channel protein. Given that \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            activates at voltages within the pacemaker\u2019s diastolic depolarization, inhibition of \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            in part may account for autoimmune-associated sinus bradycardia. In addition, Bay K8644 rescue of \u03b1\n            <jats:sub>1D<\/jats:sub>\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Ca-L<\/jats:sub>\n            inhibition opens new directions in the development of pharmacotherapeutic approaches in the management of CHB.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.104.517326","type":"journal-article","created":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T00:25:45Z","timestamp":1118103945000},"page":"3034-3041","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":78,"title":["Novel Molecular Mechanism Involving \u03b1\n            <sub>1D<\/sub>\n            (Cav1.3) L-Type Calcium Channel in Autoimmune-Associated Sinus Bradycardia"],"prefix":"10.1161","volume":"111","author":[{"given":"Yongxia","family":"Qu","sequence":"first","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System (Y.Q., G.B., Y.Y., M.B.), SUNY Downstate Medical Center (Y.Q., G.B., M.B.), and NYU School of Medicine (M.B.), New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghayath","family":"Baroudi","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System (Y.Q., G.B., Y.Y., M.B.), SUNY Downstate Medical Center (Y.Q., G.B., M.B.), and NYU School of Medicine (M.B.), New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuankun","family":"Yue","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System (Y.Q., G.B., Y.Y., M.B.), SUNY Downstate Medical Center (Y.Q., G.B., M.B.), and NYU School of Medicine (M.B.), New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Boutjdir","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System (Y.Q., G.B., Y.Y., M.B.), SUNY Downstate Medical Center (Y.Q., G.B., M.B.), and NYU School of Medicine (M.B.), New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Buyon JP. 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