Spatial Distribution of Calcium Sparks Determines Their Ability to Induce Afterdepolarizations in Human Atrial Myocytes.

Analysis of the spatio-temporal distribution of calcium sparks showed a preferential increase in sparks near the sarcolemma in atrial myocytes from patients with atrial fibrillation (AF), linked to higher ryanodine receptor (RyR2) phosphorylation at s2808 and lower calsequestrin-2 levels. Mathematical modeling, incorporating modulation of RyR2 gating, showed that only the observed combinations of RyR2 phosphorylation and calsequestrin-2 levels can account for the spatio-temporal distribution of sparks in patients with and without AF. Furthermore, we demonstrate that preferential calcium release near the sarcolemma is key to a higher incidence and amplitude of afterdepolarizations in atrial myocytes from patients with AF.

Monitoring and Analysis of COVID-19 Pandemic: The Need for an Empirical Approach.

The current worldwide pandemic produced by coronavirus disease 2019 (COVID-19) has changed the paradigm of mathematical epidemiology due to the high number of unknowns of this new disease. Thus, the empirical approach has emerged as a robust tool to analyze the actual situation carried by the countries and also allows us to predict the incoming scenarios. In this paper, we propose three empirical indexes to estimate the state of the pandemic.

Robust estimation of diagnostic rate and real incidence of COVID-19 for European policymakers.

Policymakers need clear, fast assessment of the real spread of the COVID-19 epidemic in each of their respective countries. Standard measures of the situation provided by the governments include reported positive cases and total deaths. While total deaths indicate immediately that countries like Italy and Spain had the worst situation as of mid-April, 2020, reported cases alone do not provide a complete picture of the situation.

Buffering and total calcium levels determine the presence of oscillatory regimes in cardiac cells.

Calcium oscillations and waves induce depolarization in cardiac cells which are believed to cause life-threathening arrhythimas. In this work, we study the conditions for the appearance of calcium oscillations in both a detailed subcellular model of calcium dynamics and a minimal model that takes into account just the minimal ingredients of the calcium toolkit. To avoid the effects of homeostatic changes and the interaction with the action potential we consider the somewhat artificial condition of a cell without pacing and with no calcium exchange with the extracellular medium.

Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes.

Transverse and axial tubules (TATS) are an essential ingredient of the excitation-contraction machinery that allow the effective coupling of L-type Calcium Channels (LCC) and ryanodine receptors (RyR2). They form a regular network in ventricular cells, while their presence in atrial myocytes is variable regionally and among animal species We have studied the effect of variations in the TAT network using a bidomain computational model of an atrial myocyte with variable density of tubules. At each z-line the t-tubule length is obtained from an exponential distribution, with a given mean penetration length.

Computational Model of Calcium Signaling in Cardiac Atrial Cells at the Submicron Scale.

In cardiac cells, calcium is the mediator of excitation-contraction coupling. Dysfunctions in calcium handling have been identified as the origin of some cardiac arrhythmias. In the particular case of atrial myocytes, recent available experimental data has found links between these dysfunctions and structural changes in the calcium handling machinery (ryanodine cluster size and distribution, t-tubular network, etc).