@article{3f15918651ce4248b0408046921d8cdf,
title = "Late Ca2+ Sparks and Ripples During the Systolic Ca2+ Transient in Heart Muscle Cells",
abstract = "Rationale: The development of a refractory period for Ca2+ spark initiation after Ca2+ release in cardiac myocytes, should inhibit further Ca2+ release during the action potential (AP) plateau. However, Ca2+release sites that did not initially activate, or which have prematurely recovered from refractoriness might release Ca2+ later during the AP and alter the cell-wide Ca2+ transient.Objective: To investigate the possibility of late Ca2+ spark (LCS) activity in intact isolated cardiac myocytes using fast confocal line scanning with improved confocality and signal to noise.Methods and Results: We recorded Ca2+ transients from cardiac ventricular myocytes isolated from rabbit hearts. APs were produced by electrical stimulation and rapid solution changes were used to modify the Ltype Ca2+ current. After the upstroke of the Ca2+ transient, late Ca2+ sparks (LCS) were detected which had increased amplitude compared to diastolic Ca2+ sparks. LCS are triggered by both L-type Ca2+ channel activity during the action potential plateau, as well as by the increase of cytosolic Ca2+ associated with the Ca2+ transient itself. Importantly, a mismatch between SR load and L-type Ca2+ trigger can increase the number of LCS. The likelihood of triggering a LCS also depends on recovery from refractoriness that appears after prior activation. Consequences of LCS include a reduced rate of decline of the Ca2+ transient and, if frequent, formation of microscopic propagating Ca2+ release events (Ca2+ ripples). Ca2+ ripples resemble Ca2+ waves in terms of local propagation velocity but spread for only a short distance due to limited regeneration.Conclusions: These new types of Ca2+ signalling behaviour extend our understanding of Ca2+ mediated signalling. LCS may provide an arrhythmogenic substrate by slowing the Ca2+ transient decline as well as by amplifying maintained Ca2+ current effects on intracellular Ca2+ and consequently Na+/Ca2+ exchange current.",
keywords = "Heart, Ca2+ sparks, excitation-contraction coupling, cytosolic Ca2+, calcium signaling, cardiomyocyte, cardiac myocyte",
author = "Ewan Fowler and Cherrie Kong and Jules Hancox and Mark Cannell",
note = "epub 24 December 2017",
year = "2018",
month = feb,
day = "1",
doi = "10.1161/CIRCRESAHA.117.312257",
language = "English",
volume = "122",
pages = "473--478",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "3",
}