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.

Dissecting Cellular Mechanisms of Long-Chain Acylcarnitines-Driven Cardiotoxicity: Disturbance of Calcium Homeostasis, Activation of Ca2+-Dependent Phospholipases, and Mitochondrial Energetics Collapse

“…With time, sparks frequency raised two- to threefold, and the areas occupied with high frequency sparks substantially enlarged ( Figure 1 A, t = 60–63 s and t = 85–88 s). It is believed that Ca 2+ -sparks may underlie both the initiation and propagation of slow Ca 2+ -waves [ 28 , 29 ].…”

“…Previous studies have indicated that close localization between SR and mitochondria may create functional interplay among them in limited microdomains with the exchange of Ca 2+ [ 32 , 33 , 34 ], providing rapid Ca 2+ buffering in mitochondria and limiting [Ca 2+ ] i [ 33 ]. As for pathophysiological relevance, it has been hypothesized that the interplay between SR and mitochondria may be involved in the induction of aberrant Ca 2+ -sparks, propagation of Ca 2+ -waves [ 29 ], and may increase the susceptibility for mPTP in the areas of close contacts of mitochondria with SR [ 35 , 36 , 37 , 38 ].…”

High-intensity intermittent training is as effective as moderate continuous training, and not deleterious, in cardiomyocyte remodeling of hypertensive rats

“…In their experiments, sparks were measured on the cells "at rest" but previously stimulated (1 Hz), and consequently the mechanisms underlying the release and recapture of calcium ions may be different (15,27).…”

Lessons from the Endoplasmic Reticulum Ca2+ Transporters—A Cancer Connection

“…For instance, Ca 2+ spikes at the micro-molar range are commonly observed in the apical pole of pancreatic acinar cells to assist in limited exocytosis and secretion of zymogen granules in response to low IP 3 stimulation [ 60 , 61 ]. In cardiac myocytes, the opening of voltage-gated L-type Ca 2+ channels caused by membrane depolarization increases intracellular Ca 2+ level, triggering the opening of RyR2 and subsequent Ca 2+ sparks, an essential element in maintaining excitation-contraction coupling in healthy cardiac functions [ 62 ]. Moreover, Ca 2+ blips, also known as “triggering events” for Ca 2+ puffs, are formed by small, transient Ca 2+ elevations associated with the opening of a single IP 3 R channel.…”