Role of Calcium Channels in Congenital Heart Block

Abstract

Congenital heart block (CHB) is a conduction abnormality that affects hearts of foetuses and/or newborn to mothers with autoantibodies reactive with the intracellular soluble ribonucleoproteins 48‐kD La, 52‐kD Ro and 60‐kD Ro. CHB carries substantial mortality and morbidity, with more than 60% of affected children requiring lifelong pacemakers. Several hypotheses have been proposed to explain the pathogenesis of CHB. These can be grouped under three main hypotheses: Apoptosis, Serotoninergic and Ca channel hypothesis. Here, we discuss these hypotheses and provide recent scientific thinking that will most likely dominate the future of this field of research.

Isolated atrioventricular block of unknown origin in adults and anti-Ro/SSA antibodies: Clinical evidence, putative mechanisms, and therapeutic implications

“…4 However, specific differences between adult and fetal heart electrophysiology may account for the significant age-related differences observed.…”

“…4 Furthermore, Xiao et al 5 showed that in the heart of pups born to Ro/SSA-52kD immunized rabbits, L-type channels were downregulated. Moreover, Salomonsson et al 6 demonstrated that anti-Ro/ SSA-52kD from positive patients bound cultured cardiomyocytes and markedly dysregulated calcium intracellular homeostasis, eventually resulting in intracellular calcium accumulation and apoptotic cell death.…”

“…1,4,20 The functional consequences of reduced calcium channel reserve on the cardiomyocyte membrane are amplified by the concomitant fact that, in the fetal heart, the sarcoplasmic reticulum is structurally and functionally underdeveloped, resulting in limited calcium-loading capacity. Thus, in fetal more than in adult cardiomyocytes, excitation-contraction coupling is critically dependent on transsarcolemmal calcium entry through L-type calcium channels.…”

Pathogenic effects of maternal antinuclear antibodies during pregnancy in women with lupus

“…38,39 Ro52 possesses two sequences at the carboxyl terminus (residues 365-382 and 380-396) that share partial homology with the 5-HT4A serotonin receptor. 40 These receptors are involved in cardiovascular stimulation and consequently participate in arrhythmias; therefore, 5-HT4A receptors are widely expressed in the atrial tissue of fetal hearts. 41 These molecular data are of clinical importance for understanding the pathophysiology of CHB.…”

Comment on “Absence of an association between anti-Ro antibodies and prolonged QTc interval in systemic sclerosis: A multicenter study of 689 patients”

“…Indeed, a number of experimental studies clearly demonstrated the ability of anti-Ro/SSA antibodies to directly bind to L-type calcium channels and significantly inhibit the calcium currents [3]. It is well recognized that calcium and potassium channels have opposite effects on action potential duration (APD), and thus on QTc interval.…”