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ABSTRACT: Cells often measure their local environment via the interaction of diffusible chemical signals with cell surface receptors. At the level of a single receptor, this process is inherently stochastic, but cells can contain many such receptors which can reduce the variability in the detected signal by suitable averaging. Here, we use explicit Monte Carlo simulations and analytical calculations to characterize the noise level as a function of the number of receptors. We show that the residual level approaches zero and that the correlation time, i.e., the waiting time needed to obtain statistically independent data, diverges, both for large receptor numbers. This result has important implications for such processes as eukaryotic chemotaxis.
Physical Review E 07/2007; 75(6 Pt 1):061905. · 2.26 Impact Factor
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ABSTRACT: During calcium-induced calcium-release, the ryanodine receptor (RyR) opens and releases large amounts of calcium from the sarcoplasmic reticulum into the cytoplasm of the myocyte. Recent experiments have suggested that cooperativity between the four monomers comprising the RyR plays an important role in the dynamics of the overall receptor. Furthermore, this cooperativity can be affected by the binding of FK506 binding protein, and hence, modulated by adrenergic stimulation through the phosphorylating action of protein kinase A. This has important implications for heart failure, where it has been hypothesized that RyR hyperphosphorylation, resulting in a loss of cooperativity, can lead to a persistent leak and a reduced sarcoplasmic-reticula content. In this study, we construct a theoretical model that examines the cooperativity via the assumption of an allosteric interaction between the four subunits. We find that the level of cooperativity, regulated by the binding of FK506 binding-protein, can have a dramatic effect on the excitation-contraction coupling gain and that this gain exhibits a clear maximum. These findings are compared to currently available data from different species and allows for an evaluation of the aforementioned heart-failure scenario.
Biophysical Journal 12/2005; 89(5):3017-25. · 3.65 Impact Factor
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ABSTRACT: The opening of inositol (1,4,5)-triphosphate (IP(3)) receptors, clustered at discrete sites on the endoplasmic reticulum, can lead to large-scale intracellular calcium waves. Recent experiments in Xenopus oocytes have shown that the inter-wave intervals for these waves have a standard deviation that is much smaller than their mean and that the background calcium concentration exhibits a slow rise during the interwave interval. Using a simple mathematical model, we examine the possibility that this slow rise increases the cooperativity between the openings of the clusters. We find that our model, coupled to the usual assumption that the pumps on the endoplasmic reticulum are activated instantaneously, is unable to explain the observed data: the clusters are found to fire independently and the inter-wave interval distribution is a Poisson distribution with a standard deviation that is approximately equal to its mean. On the other hand, we find that incorporating pumps that slowly activate leads to a slow increase in the background calcium concentration which makes global events progressively more likely to occur. We show that this cooperativity results in much smaller standard deviations and inter-wave interval distributions that are clearly not Poisson distributions.
Physical Biology 07/2004; 1(1-2):27-34. · 2.60 Impact Factor
