Ryanodine receptor sensitization results in abnormal calcium signaling in airway smooth muscle cells.

Intracellular Ca(2+) dynamics of airway smooth muscle cells (ASMCs) are believed to play a major role in airway hyperresponsiveness and remodeling in asthma. Prior studies have underscored a prominent role for inositol 1,4,5-triphosphate (IP3) receptors in normal agonist-induced Ca(2+) oscillations, whereas ryanodine receptors (RyRs) appear to remain closed during such Ca(2+) oscillations, which mediate ASMC contraction. Nevertheless, RyRs have been hypothesized to play a role in hyperresponsive Ca(2+) signaling.

The role of inflammation resolution speed in airway smooth muscle mass accumulation in asthma: insight from a theoretical model.

Despite a large amount of in vitro data, the dynamics of airway smooth muscle (ASM) mass increase in the airways of patients with asthma is not well understood. Here, we present a novel mathematical model that describes qualitatively the growth dynamics of ASM cells over short and long terms in the normal and inflammatory environments typically observed in asthma. The degree of ASM accumulation can be explained by an increase in the rate at which ASM cells switch between non-proliferative and proliferative states, driven by episodic inflammatory events.

Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model.

Intracellular Ca(2+) dynamics of airway smooth muscle cells (ASMC) mediate ASMC contraction and proliferation, and thus play a key role in airway hyper-responsiveness (AHR) and remodelling in asthma. We evaluate the importance of store-operated Ca(2+) entry (SOCE) in these Ca(2+) dynamics by constructing a mathematical model of ASMC Ca(2+) signaling based on experimental data from lung slices. The model confirms that SOCE is elicited upon sufficient Ca(2+) depletion of the sarcoplasmic reticulum (SR), while receptor-operated [Ca(2+) entry (ROCE) is inhibited in such conditions.

Spatiotemporal organization of Ca dynamics: a modeling-based approach.

Calcium is a ubiquitous second messenger that mediates vital physiological responses such as fertilization, secretion, gene expression, or apoptosis. Given this variety of processes mediated by Ca(2+), these signals are highly organized both in time and space to ensure reliability and specificity. This review deals with the spatiotemporal organization of the Ca(2+) signaling pathway in electrically nonexcitable cells in which InsP(3) receptors are by far the most important Ca(2+) channels.

Bifurcation analysis of a periodically forced relaxation oscillator: differential model versus phase-resetting map.

We compare the dynamics of the periodically forced FitzHugh-Nagumo oscillator in its relaxation regime to that of a one-dimensional discrete map of the circle derived from the phase-resetting response of this oscillator (the "phase-resetting map"). The forcing is a periodic train of Gaussian-shaped pulses, with the width of the pulses much shorter than the intrinsic period of the oscillator. Using numerical continuation techniques, we compute bifurcation diagrams for the periodic solutions of the full differential equations, with the stimulation period being the bifurcation parameter.