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(Circulation. 2001;103:1599.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Direct Inhibition of Expressed Cardiac L- and T-Type Calcium Channels by IgG From Mothers Whose Children Have Congenital Heart Block

Guang-Qian Xiao, MD; Keli Hu, MD, PhD; Mohamed Boutjdir, PhD

From the Molecular and Cellular Cardiology Program, New York Harbor Healthcare System and SUNY Health Science Center, Brooklyn, NY.

Correspondence to Dr Mohamed Boutjdir, R&D Office (151), Molecular and Cellular Cardiology Program, New York Harbor Healthcare System, 800 Poly Place, Brooklyn, NY 11209. E-mail mohamed.boutjdir{at}med.va.gov

Background—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.

Methods and Results—The 2-electrode voltage-clamp technique was used to record currents via L-type (I_Ba-_1C or I_Ba-_1C+ß_2a+₂/) and T-type (I_Ba-_1H) Ca channels, Na channels (I_Na-hH1), and K channels (I_Ks-minK+KvLQT1) expressed in Xenopus oocytes. Positive IgG (350 µg/mL) inhibited I_Ba-_1C by 50.6±4.7% (P<0.01) and I_Ba-_1C+ß_2a+₂/ by 50.9±4.2% (P<0.01); I_Ba-_1H was reduced by 18.9±1.0% (P<0.01). Immunoblot data show cross-reactivity of positive IgG with _1C subunit. Pretreatment of oocytes with atropine (1 µmol/L) or acetylcholine (10 µmol/L) did not affect the inhibitory effect of IgG on I_Ba-_1C and I_Ba-_1C+ß_2a+₂/ (P<0.05). Positive IgG had no effect, however, on either I_Na-hH1 or I_Ks-minK+KvLQT1.

Conclusions—Positive IgG inhibited expressed L-type I_Ba and cross-reacted with the _1C subunit in Xenopus oocytes, providing strong evidence that maternal antibodies interact directly with the pore-forming ₁-subunit of Ca channels. In addition, we show for the first time that positive IgG also inhibited T-type I_Ba but not I_Na-hH1 or I_Ks-minK+KvLQT1. This could provide, in part, the ionic basis of sinus bradycardia reported in animal models of CHB and clinically in humans.

Key Words: antibodies • ion channels • electrophysiology

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