Autoantibodies from mothers of children with congenital heart block downregulate cardiac L-type ca channels

Congenital heart block (CHB) affects offspring of mothers with autoantibodi es (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that matern al anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcole mma, recognize human L-type Ca channel alpha (1C)-protein and functionally inhibit expressed current in oocytes injected with alpha (1C) cRNA and Purk inje L-type Ca current, Furthermore, cardiac myocytes from pups born to SSA /Ro-immunized mice exhibited reduced L-type Ca current density. All togethe r, the data establish that L-type calcium channel is a target for maternal antibodies and may provide a functional basis for the electrocardiographic abnormalities seen in infants with CHB. (C) 2001 Academic Press.