{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T16:41:25Z","timestamp":1794328885660,"version":"4.9.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,3,20]]},"abstract":"\n Background<\/jats:italic>\n \u2014Congenital heart block (CHB) is a disease that affects the offspring of mothers with autoimmune diseases. We recently reported that maternal sera containing antibodies against SSA\/Ro and SSB\/La ribonucleoproteins (positive IgG) inhibited L-type Ca current in isolated cardiac myocytes and induced sinus bradycardia in a murine model of CHB. The direct interaction of positive IgG with L-type Ca channel proteins and the possible inhibition of T-type Ca current that could account for the sinus bradycardia remain unknown.\n <\/jats:p>\n \n Methods and Results<\/jats:italic>\n \u2014The 2-electrode voltage-clamp technique was used to record currents via L-type (\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1C<\/jats:sub>\n or\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1C<\/jats:sub>\n +\u03b2\n 2a<\/jats:sub>\n +\u03b1\n 2<\/jats:sub>\n \/\u03b4) and T-type (\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1H<\/jats:sub>\n ) Ca channels, Na channels (\n I<\/jats:italic>\n Na<\/jats:sub>\n -hH1), and K channels (\n I<\/jats:italic>\n Ks<\/jats:sub>\n -minK+KvLQT1) expressed in\n Xenopus<\/jats:italic>\n oocytes. Positive IgG (350 \u03bcg\/mL) inhibited\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1C<\/jats:sub>\n by 50.6\u00b14.7% (\n P<\/jats:italic>\n <0.01) and\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1C<\/jats:sub>\n +\u03b2\n 2a<\/jats:sub>\n +\u03b1\n 2<\/jats:sub>\n \/\u03b4 by 50.9\u00b14.2% (\n P<\/jats:italic>\n <0.01);\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1H<\/jats:sub>\n was reduced by 18.9\u00b11.0% (\n P<\/jats:italic>\n <0.01). Immunoblot data show cross-reactivity of positive IgG with \u03b1\n 1C<\/jats:sub>\n subunit. Pretreatment of oocytes with atropine (1 \u03bcmol\/L) or acetylcholine (10 \u03bcmol\/L) did not affect the inhibitory effect of IgG on\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1C<\/jats:sub>\n and\n I<\/jats:italic>\n Ba<\/jats:sub>\n -\u03b1\n 1C<\/jats:sub>\n +\u03b2\n 2a<\/jats:sub>\n +\u03b1\n 2<\/jats:sub>\n \/\u03b4 (\n P<\/jats:italic>\n <0.05). Positive IgG had no effect, however, on either\n I<\/jats:italic>\n Na<\/jats:sub>\n -hH1 or\n I<\/jats:italic>\n Ks<\/jats:sub>\n -minK+KvLQT1.\n <\/jats:p>\n \n Conclusions<\/jats:italic>\n \u2014Positive IgG inhibited expressed L-type\n I<\/jats:italic>\n Ba<\/jats:sub>\n and cross-reacted with the \u03b1\n 1C<\/jats:sub>\n subunit in\n Xenopus<\/jats:italic>\n oocytes, providing strong evidence that maternal antibodies interact directly with the pore-forming \u03b1\n 1<\/jats:sub>\n -subunit of Ca channels. In addition, we show for the first time that positive IgG also inhibited T-type\n I<\/jats:italic>\n Ba<\/jats:sub>\n but not\n I<\/jats:italic>\n Na<\/jats:sub>\n -hH1 or\n I<\/jats:italic>\n Ks<\/jats:sub>\n -minK+KvLQT1. This could provide, in part, the ionic basis of sinus bradycardia reported in animal models of CHB and clinically in humans.\n <\/jats:p>","DOI":"10.1161\/01.cir.103.11.1599","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:09:32Z","timestamp":1339459772000},"page":"1599-1604","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":112,"title":["Direct Inhibition of Expressed Cardiac L- and T-Type Calcium Channels by IgG From Mothers Whose Children Have Congenital Heart Block"],"prefix":"10.1161","volume":"103","author":[{"given":"Guang-Qian","family":"Xiao","sequence":"first","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, New York Harbor Healthcare System and SUNY Health Science Center, Brooklyn, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keli","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, New York Harbor Healthcare System and SUNY Health Science Center, Brooklyn, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Boutjdir","sequence":"additional","affiliation":[{"name":"From the Molecular and Cellular Cardiology Program, New York Harbor Healthcare System and SUNY Health Science Center, Brooklyn, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1177\/096120339500400207"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-120-7-199404010-00003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(95)90621-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199609000-00016"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.24.9479"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03446.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(05)70313-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.80.3.354"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.14.1914"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117025"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199807000-00002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1139\/y96-108"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.83.1.103"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/384080a0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.97.7.640"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(98)93032-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.50.30036"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.8.14.7958624"},{"key":"e_1_3_2_21_2","unstructured":"Deleted in proof."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp021029"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1139"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199102000-00014"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199308000-00019"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.27.3.426"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.1.88"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(86)90064-0"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100249900017"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.54.11.904"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.141.5.1480"},{"key":"e_1_3_2_32_2","first-page":"454","volume":"78","year":"1989","unstructured":"Baboonian C, Venables PJ, Booth J, et al. 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