2014
DOI: 10.1152/ajpheart.00515.2013
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Are SR Ca content fluctuations or SR refractoriness the key to atrial cardiac alternans?: insights from a human atrial model

Abstract: Despite the important role of electromechanical alternans in cardiac arrhythmogenesis, its molecular origin is not well understood. The appearance of calcium alternans has often been associated to fluctuations in the sarcoplasmic reticulum (SR) Ca loading. However, cytosolic calcium alternans observed without concurrent oscillations in the SR Ca content suggests an alternative mechanism related to a dysfunction in the dynamics of the ryanodine receptor (RyR2). We have investigated the effect of SR release refr… Show more

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Cited by 44 publications
(52 citation statements)
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“…The study of Shkryl et al [54] demonstrated that in rabbit atrial myocytes a large amplitude CaT indeed prolongs RyR refractoriness and that the kinetics of RyR recovery from inactivation is a key factor in the generation of Ca 2+ alternans. This hypothesis also found support from in silico simulations [68]. …”
Section: Putative Mechanisms Of Alternanssupporting
confidence: 72%
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“…The study of Shkryl et al [54] demonstrated that in rabbit atrial myocytes a large amplitude CaT indeed prolongs RyR refractoriness and that the kinetics of RyR recovery from inactivation is a key factor in the generation of Ca 2+ alternans. This hypothesis also found support from in silico simulations [68]. …”
Section: Putative Mechanisms Of Alternanssupporting
confidence: 72%
“…4B) [72]. Computer simulations using cell models with and without t-tubules have predicted significant differences in possible alternans mechanisms [23,68,73]. The cardiac cell models lacking t-tubules exhibited higher likelihood to develop Ca 2+ alternans and pointed towards the role of Ca 2 + diffusion, inhomogeneity in [Ca 2+ ] i [73] and RyR refractoriness [68] in the process.…”
Section: Differences Between Atrial and Ventricular Alternansmentioning
confidence: 99%
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“…In order to reduce Eqs. (14), (15) to an autonomous problem that can be analyzed by AUTO, we rewrite the forcing in terms of the periodic solutions of an auxiliary autonomous ordinary differential equations (ODE) system 27,32 . We represent the calcium current I CaL as a pulse of duration ∆t = 10ms, that starts with a delay t c1 after each T period and with a halftime steep value, m, to its maximum value I CaLmax (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…It is generally agreed that bi-directional coupling between these parameters underlies the development of cardiac alternans, 18,19 however it has remained a matter of debate which one of the 2 parameters, when its regulation becomes disturbed, is the primary cause of cardiac alternans. While computational studies have generated arguments in favor of both parameters ([Ca 2C ] i or V m ), 9,[24][25][26] experimental studies have provided growing evidence that alternans are initiated by disturbances of intracellular Ca 2C handling. [15][16][17]27,28 Major support for this hypothesis came from the demonstration that CaT alternans can be elicited in voltage-clamped ventricular myocytes even when beat-to-beat changes of V m were kept constant.…”
Section: Discussionmentioning
confidence: 99%