Calcium Sparks in the Heart: Dynamics and Regulation

Abstract

Calcium (Ca²⁺) plays a central role in the contraction of the heart. It is the bi-directional link between electrical excitation of the heart and contraction. Electrical excitation initiates Ca²⁺influx across the sarcolemma and T-tubular membrane that triggered calcium release from the sarcoplasmic reticulum. Ca²⁺sparks are the elementary events of calcium release from the sarcoplasmic reticulum. Therefore, understanding the dynamics of Ca²⁺sparks is essential for understanding the function of the heart. To this end, numerous experimental and computational studies have focused on this topic, exploring the mechanisms of calcium spark initiation, termination, and regulation and what role these play in normal and patho-physiology. The proper understanding of Ca²⁺ spark regulation and dynamics serves as the foundation for our insights into a multitude of pathological conditions may develop that can be the result of structural and/or functional changes at the cellular or subcellular level. Computational modeling of Ca²⁺ spark dynamics has proven to be a useful tool to understand Ca²⁺ spark dynamics. This review addresses our current understanding of Ca²⁺ sparks and how synchronized SR Ca²⁺ release, in which Ca²⁺ sparks is a major pathway, is linked to the different cardiac diseases, especially arrhythmias.

Keywords: arrhythmia; calcium; heart; sparks.

Figure 1

A schematic diagram of calcium-induced calcium-release mechanism in a cardiac myocyte. (A) the distribution of SR in the sarcomere, (B) details of the dyad and Ca²⁺ dynamics.

Figure 2

Simulation with sticky cluster model incorporated into model for excitation-contraction coupling in the rat ventricular myocyte. (A) dyadic subspace [Ca²⁺] showing Ca²⁺ sparks and (B) dyadic subspace [Ca²⁺] showing Ca²⁺ quarks, (C) Dynamics of jSR Ca²⁺ release, (D) Number of RyR2 openings,

Figure 3

Simulated Ca²⁺ spark. (A) Linescan of Ca²⁺ spark, (B) Linescan of Ca²⁺ sparks during an action potential, (C) Spatial profile at different times after peak (bk=black at 0 ms, r = red at 2 ms, g = green at 6 ms, bl = blue at 10 ms and br = brown at 20 ms).

Figure 4

Simulation with sticky cluster model incorporated into model for excitation-contraction coupling in the rat ventricular myocyte to explore heart failure. In the panes black = control, green = orphaning – T-tubular rearrangement, red = changes in gene expression and post-translational modification with heart failure blue = red + T-tubular rearrangement, and (A) Cytosolic [Ca²⁺], (B) SR [Ca²⁺], (C), subspace [Ca²⁺]_ds, (D) Action potential.