Frequency of elemental events of intracellular<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:msup><mml:mi mathvariant="normal">Ca</mml:mi><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:math>dynamics

Thul, Ruediger; Falcke, Martin

doi:10.1103/physreve.73.061923

Cited by 35 publications

(20 citation statements)

References 32 publications

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“…In this paper we will apply numerical and analytic approaches to address these questions. Our approach builds on the work of several authors, in particular Hinch [19] and Thul et al [20] (see also [17], [21]–[26] for similar approaches), who have applied the theory of stochastic processes to describe subcellular Ca signaling. As a starting point we will first determine the timing statistics of spontaneous Ca sparks within a single isolated CRU at a fixed SR Ca load.…”

Section: Introductionmentioning

confidence: 99%

The Timing Statistics of Spontaneous Calcium Release in Cardiac Myocytes

2013

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A variety of cardiac arrhythmias are initiated by a focal excitation that disrupts the regular beating of the heart. In some cases it is known that these excitations are due to calcium (Ca) release from the sarcoplasmic reticulum (SR) via propagating subcellular Ca waves. However, it is not understood what are the physiological factors that determine the timing of these excitations at both the subcellular and tissue level. In this paper we apply analytic and numerical approaches to determine the timing statistics of spontaneous Ca release (SCR) in a simplified model of a cardiac myocyte. In particular, we compute the mean first passage time (MFPT) to SCR, in the case where SCR is initiated by spontaneous Ca sparks, and demonstrate that this quantity exhibits either an algebraic or exponential dependence on system parameters. Based on this analysis we identify the necessary requirements so that SCR occurs on a time scale comparable to the cardiac cycle. Finally, we study how SCR is synchronized across many cells in cardiac tissue, and identify a quantitative measure that determines the relative timing of SCR in an ensemble of cells. Using this approach we identify the physiological conditions so that cell-to-cell variations in the timing of SCR is small compared to the typical duration of an SCR event. We argue further that under these conditions inward currents due to SCR can summate and generate arrhythmogenic triggered excitations in cardiac tissue.

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Section: Introductionmentioning

confidence: 99%

The Timing Statistics of Spontaneous Calcium Release in Cardiac Myocytes

2013

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“…The method used here presents an approximation of (Gillespie 1977) and works well for small time steps and a limited number of states. For more detail, I refer the reader to (Thul and Falcke 2006;2007;Higgins et al 2009 …”

Section: Methodsmentioning

confidence: 99%

Time to Blip—Stochastic Simulation of Single Channel Opening

Thul

2014

Cold Spring Harb Protoc

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The stochastic dynamics of the inositol-1,4,5-trisphosphate (IP3) receptor (IP3R) is key to understanding a wide range of observed calcium (Ca 2+ ) signals (Falcke 2004). The stochastic nature results from the constant binding and unbinding of Ca 2+ and IP3 to and from their respective binding sites and is especially important in the initiation of a Ca 2+ puff, i.e. the release of Ca 2+ through a cluster of IP3Rs. Once the first IP3R opens, the Ca 2+ concentration rises significantly around the ion channel and hence increases the open probability for neighboring IP3Rs. In turn this may trigger the activation of further receptors giving rise to a Ca 2+ puff (Thul et al. 2009;Thurley et al. 2012). In this protocol, we determine the time that it takes for a single IP3R to open from rest. We explicitly take into account the tetrameric structure of the IP3R and the fact that multiple subunits need to be active before the channel opens (Bezprozvanny et al. 1991;Watras et al. 1991). We develop code for a stochastic simulation of the IP3R and simulate it using the software package Matlab (Attaway 2011). This protocol demonstrates the basic form of a stochastic simulation algorithm and may serve as a starting point to investigate more complex gating dynamics.

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“…Thus, whole-cell calcium release is inherently spatially localized and stochastic in nature. Recent modeling efforts have focused on calcium regulation at a small patch-size or a release unit level (Greenstein et al, 2006;Hinch, 2004;Hinch et al, 2004;Tanskannen et al, 2007;Thul and Falcke, 2006). In this paper, we build upon these previous efforts and derive a minimal model for a calcium release unit (CRU).…”

Section: Introductionmentioning

confidence: 99%