Cardiovascular Disease: Calcium Channel Anomalies

Abstract

Cardiomyocyte calcium homeostasia is essential to cardiomyocyte excitation and contraction. Calcium enters through voltage-dependant calcium channels (I_Cal) and activates sarcoplasmic reticulum (SR) membrane ryanodine receptors (RyRs) triggering a massive release of stored Ca²⁺ essential to actine-myosine cross-bridging and sarcomere shortening. Calcium is than reabsorbed by the SR through SERCA and expelled from the cell by sodium/calcium exchanger (NCX). Some acquired heart diseases cause calcium homeostasia dysfunction: (1) heart failure causes reduced SERCA calcium uptake and porous RyRs. The ensuing calcium overload leads to NCX over-activation and arrhythmia triggering “late after-depolarizations”-generating cytosolic sodium increase. (2) Bordering infarct zones have disorganized RyR coupling and reduced SERCA activity responsible for potentially pro-arrhythmogenic situations. (3) Atrial fibrillation, through lessened I_Cal activity, leads to shortened action potential and contractile dysfunction. Some congenital heart diseases stem from abnormalities in the expression of calcium homeostasia agents: Some forms of long QT syndromes are linked to slow inactivation of I_Cal and persistent phase 2 plateau, with a heightened risk of ventricular arrhythmia. Heterogeneous distribution of I_to current potassium channel amplified by failures in the inward I_Cal depolarizing currents creates an epicardial-endocardial repolarization gradient also responsible for some forms of Brugada and short QT syndromes. Calcium leaks due to RyR abnormalities or of its regulation proteins can activate LAD triggering NCX over activation causing Polymorphic ventricular tachycardia. Some congenital atrial ventricular blocks are caused by impeded calcium channel activities of foetus hearts due to anti-bodies of lupus-affected mothers.