Direct inhibition of expressed cardiac L- and T-type calcium channels by IgG from mothers whose children have congenital heart block

Congenital 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. The 2-electrode voltage-clamp technique was used to record currents via L-type (I(Ba)-alpha(1C) or I(Ba)-alpha(1C)+beta(2a)+alpha(2)/delta) and T-type (I(Ba)-alpha(1H)) Ca channels, Na channels (I(Na)-hH1), and K channels (I(Ks)-minK+KvLQT1) expressed in Xenopus oocytes. Positive IgG (350 microgram/mL) inhibited I(Ba)-alpha(1C) by 50.6+/-4.7% (P