Search

Dysregulated intracellular Ca2+ signaling is implicated in a variety of cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia. Spontaneous diastolic Ca2+ release (DCR) can induce arrhythmogenic plasma membrane depolarizations, although the mechanism responsible for DCR synchronization among adjacent myocytes required for ectopic activity remains unclear. We investigated the synchronization mechanism(s) of DCR underlying untimely action potentials and diastolic contractions (DCs) in a catecholaminergic polymorphic ventricular tachycardia mouse model with a mutation in cardiac calsequestrin. We used a combination of different approaches including single ryanodine receptor channel recording, optical imaging (Ca 2+ and membrane potential), and contractile force measurements in ventricular myocytes and intact cardiac muscles. We demonstrate that DCR occurs in a temporally and spatially uniform manner in both myocytes and intact myocardial tissue isolated from cardiac calsequestrin mutation mice. Such synchronized DCR events give rise to triggered electrical activity that results in synchronous DCs in the myocardium. Importantly, we establish that synchronizationof DCR is a result of a combination of abbreviated ryanodine receptor channel refractoriness and the preceding synchronous stimulated Ca 2+ release/reuptake dynamics. Our study reveals how aberrant DCR events can become synchronized in the intact myocardium, leading to triggered activity and the resultant DCs in the settings of a cardiac rhythm disorder.

Dysregulated intracellular Ca2+ signaling is implicated in a variety of cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia. Spontaneous diastolic Ca2+ release (DCR) can induce arrhythmogenic plasma membrane depolarizations, although the mechanism responsible for DCR synchronization among adjacent myocytes required for ectopic activity remains unclear. We investigated the synchronization mechanism(s) of DCR underlying untimely action potentials and diastolic contractions (DCs) in a catecholaminergic polymorphic ventricular tachycardia mouse model with a mutation in cardiac calsequestrin. We used a combination of different approaches including single ryanodine receptor channel recording, optical imaging (Ca 2+ and membrane potential), and contractile force measurements in ventricular myocytes and intact cardiac muscles. We demonstrate that DCR occurs in a temporally and spatially uniform manner in both myocytes and intact myocardial tissue isolated from cardiac calsequestrin mutation mice. Such synchronized DCR events give rise to triggered electrical activity that results in synchronous DCs in the myocardium. Importantly, we establish that synchronizationof DCR is a result of a combination of abbreviated ryanodine receptor channel refractoriness and the preceding synchronous stimulated Ca 2+ release/reuptake dynamics. Our study reveals how aberrant DCR events can become synchronized in the intact myocardium, leading to triggered activity and the resultant DCs in the settings of a cardiac rhythm disorder.

In this work, the Graph Coloring Problem and its generalizations - the Bandwidth Coloring Problem, the Multicoloring Problem and the Bandwidth Multicoloring Problem - are studied. A Squeaky Wheel Optimization with Tabu Search heuristic is developed and experiments using benchmark geometric test cases show that the algorithm performs well for these problems and achieves results for the Bandwidth Multicoloring Problem which improve on results obtained by other researchers. Copyright 2005 ACM.

In this work, the Graph Coloring Problem and its generalizations - the Bandwidth Coloring Problem, the Multicoloring Problem and the Bandwidth Multicoloring Problem - are studied. A Squeaky Wheel Optimization with Tabu Search heuristic is developed and experiments using benchmark geometric test cases show that the algorithm performs well for these problems and achieves results for the Bandwidth Multicoloring Problem which improve on results obtained by other researchers. Copyright 2005 ACM.

In this work, the Graph Coloring Problem and its generalizations - the Bandwidth Coloring Problem, the Multicoloring Problem and the Bandwidth Multicoloring Problem - are studied. A Squeaky Wheel Optimization with Tabu Search heuristic is developed and experiments using benchmark geometric test cases show that the algorithm performs well for these problems and achieves results for the Bandwidth Multicoloring Problem which improve on results obtained by other researchers. Copyright 2005 ACM.