Opis: A coordinated functioning of beta cells within pancreatic islets is mediated by oscillatory membrane depolarization and subsequent changes in cytoplasmic calcium concentration. While gap junctions allow for intraislet information exchange, beta cells within islets form complex syncytia that are intrinsically nonlinear and highly heterogeneous. To study spatiotemporal calcium dynamics within these syncytia, we make use of computational modeling and confocal high-speed functional multicellular imaging. We show that model predictions are in good agreement with experimental data, especially if a high degree of heterogeneity in the intercellular coupling term is assumed. In particular, during the first few minutes after stimulation, the probability distribution of calcium wave sizes is characterized by a power law, thus indicating critical behavior. After this period, the dynamics changes qualitatively such that the number of global intercellular calcium events increases to the point where the behavior becomes supercritical. To better mimic normal in vivo conditions, we compare the described behavior during supraphysiological non-oscillatory stimulation with the behavior during exposure to a slightly lower and oscillatory glucose challenge. In the case of this protocol, we observe only critical behavior in both experiment and model. Our results indicate that the loss of oscillatory changes, along with the rise in plasma glucose observed in diabetes, could be associated with a switch to supercritical calcium dynamics and loss of beta cell functionality. Ključne besede:beta cells, islets of Langerhans, self-organized criticality, intercellular dynamics, calcium waves, glucose oscillations, computational model, confocal calcium imaging Objavljeno v DKUM: 23.01.2018; Ogledov: 1403; Prenosov: 375 Celotno besedilo (3,43 MB) Gradivo ima več datotek! Več...

Opis: Calcium ions are an important second messenger in living cells. Calcium signals in form of waves serve as a means of intercellular communication and thus represent a vibrant subject for experimental and theoretical investigations. Here we study the role of cellular variability on the occurrence of ▫$Ca^{2+}$▫ wave propagation in a net of diffusively coupled cells. Dynamics of individual cells is simulated by a mathematical model for ▫$Ca^{2+}$▫ oscillations. Structural diversity of cells is introduced via variations of the bifurcation parameters, which signify cell sensitivity for external stimulation. Remarkably, for sufficient values of variability ▫$Ca^{2+}$▫ waves emerge, which are mostly ordered for intermediate variability strength. We analyze the spatial profile via the autocorrelation function, which confirms aresonance-like response due to the cellular variability. Thus, the reported phenomenon is a novel observation of diversity-induced spatial coherence resonance in a tissue-like media. Ključne besede:dynamic systems, waves, calcium oscillations, resonance, diversity-induced resonance, cellular variability, coupled cells, intracellular processes Objavljeno v DKUM: 07.06.2012; Ogledov: 1789; Prenosov: 27 Povezava na celotno besedilo