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(The FASEB Journal. 2001;15:1539-1545.)
© 2001 FASEB

Down-regulation of L-type calcium channel in pups born to 52 kDa SSA/Ro immunized rabbits

GUANG-QIAN XIAO, YONGXIA QU, KELI HU and MOHAMED BOUTJDIR1

Molecular and Cellular Cardiology Program, New York Harbor HealthCare System and SUNY Health Science Center, Brooklyn, New York 11209, USA

1Correspondence: Research and Development Office (151), New York Harbor Health Care System, 800 Poly Pl., Brooklyn, NY 11209, USA. E-mail: mohamed.boutjdir{at}med.va.gov

Congenital heart block is considered a model of passively acquired autoimmune disease in which the mother generates anti-SSA/Ro and/or anti-SSB/La antibodies that cross the placenta and presumably injure the heart of developing fetus. CHB is accompanied by ECG abnormalities including AV block, sinus bradycardia, and ventricular dysfunction. Our previous data indicate that these abnormalities are caused by maternal autoantibody-mediated disturbance of L-type Ca channels. To investigate the consequence of chronic exposure of L-type Ca channels in newborn pups to maternal autoantibodies during pregnancy, we immunized female rabbits with human 52 kDa-SSA/Ro (Ro52) recombinant protein. ECG revealed that pups from the immunized group had varying degrees of conduction defects. In addition, ICaL density and protein were reduced in hearts of pups from the immunized group. Sera and purified IgG from immunized rabbits inhibited IBa recorded from oocytes with expressed {alpha}1C and ß2a subunits of L-type Ca channel. Pups born to Ro52 immunized mothers exhibited down-regulation of L-type calcium channels in heart. The data provide new insight into the pathogenesis of congenital heart block.—Xiao, C.-Q., Qu, Y., Hu, K., Boutjdir, M. Down-regulation of L-type calcium channel in pups born to 52 kDa SSA/Ro immunized rabbits.


Key Words: autoantibody • AV block • immunization • cardiac myocyte




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