Basic Sci: Calcium Regulation (Adult vs. Newborn Cardiac Myocyte)

(Images & text below are from "Balaguru et al. Curr Probl Pediatr 2000;30:5-30").

Excitation-Contraction Coupling: This is the mechanism by which electrical depolarization (excitation), results in contracton in a cardiac myocyte. Calcium acts as the secondary messenger making that coupling.

Adult Cardiac Myocyte - Calcium Regulation during contraction and relaxation:
In adult cardiac myocyte, sarcoplasmic reticulum (SR) acts as the main store of calcium. Upon depolarization of sarcolemma, a small amount of calcium enters the cell through L-type calcium channels. This small amount of calcium activates calcium release channels (Ryanodine receptors) in junctional SR - causing release of large amount of calcium into the cytoplasm from calcium stores in SR. This is called Calcium-induced Calcium Release (CICR). Increase in cytosolic calcium activates myofibrils to contract. During diastole, the fall in cytosolic calcium concentration occurs through reuptake of calcium into SR stores (~80%), calcium efflux out of the cell via Sodium-Calcium Exchanger (NCX; ~20%) and via sarcolemmal calcium pump (Ca2+-ATPase).

Neonatal cardiac myocyte - Calcium regulation during contraction and relaxation:
In neonatal cardiac myocyte, SR is sparsely developed and poorly organized. So, CICR can not fully function/support cardiac contraction in the newborn. Therefore, neonatal cardiac myocytes depend on trans-sarcolemmal influx of calcium (via L-type Calcium channels & NCX). NCX operates in "reverse" direction during systole in this situation and "forwards" during diastole. NCX plays a major role in calcium homeostasis in neonate.

Other components of Excitation-Contraction Coupling:
1) T-tubules: Invaginations of sarcolemma that help to increase the cell surface area for a given cell volume. T-tubules bring more of the sarcolemmal L-type Calcium Channels in proximity to ryanodine receptors of the SR. Thus, T-tubules enhance the efficiency of CICR. However, in neonatal cardiac myocyte, the T-tubules are absent, which impose a substantial impediment to sarcolemma to SR coupling.

2) Sodium-Pottasium Pump (Na,K-ATPase): This pump, present in sarcolemma maintains an appropriate Na gradient across the membrane. This pump exists in different isoforms. Different isoforms have different senstivity and response to cardiac glycosides - which may explain the relatively high tolerability of neonates and infants to Digoxin.

3) Calsequestrin: Major calcium storing protein inside SR. Activity of calsequestrin increases progressively with development.

4) Actin and Myosin have different isoforms for heavy and light chains - which increase in sensitivity to calcium with increasing maturity, thus influencing inotropy and lusitropy of the cardiac myocyte.

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