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

Congenital heart block is considered a model of passively acquired autoimmu ne disease in which the mother generates anti-SSA/Ro and/or anti-SSB/La ant ibodies that cross the placenta and presumably injure the heart of developi ng 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 disturbanc e of L-type Ca channels. To investigate the consequence of chronic exposure of L-type Ca channels in newborn pups to maternal autoantibodies during pr egnancy, we immunized female rabbits with human 52 kDa-SSA/Ro (Ro52) recomb inant protein. ECG revealed that pups from the immunized group had varying degrees of conduction defects. In addition, I-CaL density and protein were reduced in hearts of pups from the immunized group. Sera and purified IgG f rom immunized rabbits inhibited I-Ba recorded from oocytes with expressed a lpha (1C) and beta (2a) subunits of L-type Ca channel. Pups born to Ro52 im munized mothers exhibited down-regulation of L-type calcium channels in hea rt. The data provide new insight into the pathogenesis of congenital heart block.