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(Circulation Research. 2004;94:e32.)
© 2004 American Heart Association, Inc.

UltraRapid Communications

Functional Basis of Sinus Bradycardia in Congenital Heart Block

Keli Hu, Yongxia Qu, Yuankun Yue, Mohamed Boutjdir

From the Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, SUNY Downstate Medical Center and NYU School of Medicine, Brooklyn, NY.

Correspondence to Dr Mohamed Boutjdir, Research and Development Office (151), VA New York Harbor Healthcare System, 800 Poly Place, Brooklyn, NY 11209. E-mail mohamed.boutjdir{at}med.va.gov

Congenital heart block (CHB) is a conduction abnormality characterized by complete atrioventricular (AV) block. CHB affects fetuses and/or newborn of mothers with autoantibodies reactive with ribonucleoproteins 48-kDa SSB/La, 52-kDa SSA/Ro, and 60-kDa SSA/Ro. We recently established animal models of CHB and reported, for the first time, significant sinus bradycardia preceding AV block. This unexpected observation implies that the spectrum of conduction abnormalities extends beyond the AV node to also affect the SA node. To test this hypothesis, we investigated the functional basis of this sinus bradycardia by characterizing the effects of antibodies from mothers with CHB children (positive IgG) on ionic currents that are known to significantly contribute to spontaneous pacing in SA node cells. We recorded L- (I_Ca.L) and T- (I_Ca.T) type Ca²⁺, delayed rectifier K⁺ (I_K), hyperpolarization-activated (I_f) currents, and action potentials (APs) from young rabbit SA node cells. We demonstrated that positive IgG significantly inhibited both I_Ca.T and I_Ca.L and induced sinus bradycardia but did not affect I_f and I_K. Normal IgG from mothers with healthy children did not affect all the currents studied and APs. These results establish that IgG from mothers with CHB children causes substantial inhibition of I_Ca.T and I_Ca.L, two important pacemaker currents in rabbit SA node cells and point to both I_Ca.T and I_Ca.L as major players in the ionic mechanism by which maternal antibodies induce sinus bradycardia in CHB. These novel findings have important clinical significance and suggest that sinus bradycardia may be a potential marker in the detection and prevention of CHB. The full text of this article is available online at http://circres.ahajournals.org

Key Words: L-type calcium current • T-type calcium current • antibodies • congenital heart block

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