2 research outputs found

    Mathematical modelling and analysis of calcium oscillations in excitable and non-excitable cell lines

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    Information is transmitted from the cell surface to various specific targets in the cell via several cellular signaling pathways. Cytosolic free calcium (Ca2+)is one of the most versatile and ubiquitous intracellular messengers since it is able to regulate diverse number of functions such as proliferation, secretion, fertilization, metabolism, learning and memory. In the last couple of years, evidence has been accumulating that Ca2+ ion is able to integrate information from multiple signaling pathways and convert this information into a code which regulates events ranging from contraction to modification of gene expression (Berridge et al. 1998). It was shown that Ca2+ concentration displays oscillatory behavior in response to agonist stimulation in a variety of cells(Goldbeter 1996) and the frequency of these oscillations increases with the concentration of agonist, a behavior called frequency encoding which has led to the concept that many Ca2+-regulated processes are controlled by these codes(Berridge 1998). Although the presence of Ca2+ oscillations and the sources of Ca2+ pools involved is known in many cell types, it is yet not known how the various frequencies of Ca2+ oscillations are converted into codes that regulate the numerous cellular events. Recently a number of cellular targets that decode Ca2+ signals and are tuned to the frequency of Ca2+ oscillations have been identified. Prominent among them are calcium-calmodulin kinase II (CAM II) and protein kinase C (PKC). The objective of this work is to study and mathematically model the oxytocin and vasopressin-induced Ca2+ oscillations in cells of normal rat liver (Clone 9) and cells of pregnant human myometrium. The proposed model accounts for the receptor-controlled Ca2+ oscillations involving positive feedback leading to activation of phospholipase C (PLC) and negative feedback from PKC onto G-proteins which simulates many of the features of observed intracellular Ca2+. The model also incorporates the concept that coordinated Ca2+ signals in a group of hepatocytes require both effective gap junctions and the presence of agonist at each cell surface. Another objective of this research is to understand the relevance of frequency-encoded signals by performing an analysis of frequencies of Ca2+ oscillations using the Fast Fourier Transform and the Wavelet Transform. The validity of the model was confirmed by using statistical tests to check if the frequencies and amplitudes of the experimental Ca2+ oscillations match with those of the modelled oscillations

    Remodeling of fiber and laminar architecture of rat heart septum in a transitional normal state between pressure overload hypertrophy and failure

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    Congestive Heart Failure (CHF) is a major fatal disease today in the United States. The heart's function is a mechanical one. To diagnose and treat CHF effectively there is a need to understand at the microstructural level, the differences in the response of the myocardium to a change in its mechanical environment. Hence to assess growth and remodeling processes in the myocardium, the fiber and myolaminar structure of two groups of Dahl salt-sensitive rats were compared: low salt (LS) normal controls and a high salt (HS) group with hearts in "transitional eutrophy" defined by normal size and shape but in transition from pressure overload hypertrophy to dilated hypertrophy. To create the HS group with transitional eutrophy, we fed Dahl salt-sensitive rats, a sustained high salt diet from age 6 wks till sacrifice at age 11-13 wks. Such rats have a heart that transitions from too thick (pressure overload hypertrophy at about age 9 wks) to too thin (dilated hypertrophy at about age 15 wks to death) with a transitional period (age 11-13 wks) having normal size and shape. Fiber angles, sheet angles, number and thickness of sheets were measured in the septum at four transmural quarters (TQ1 to TQ4 with TQ1 being closest to LV and TQ4 closest to RV). A uniformity index was defined to characterize sheet angle dispersion. Upon comparison to LS controls, the HS group had normal size hearts with normal shape. However, there was a significant increase in the number of sheets, which corresponded with a significant decrease in the thickness of sheets in all quarters in HS group. Differences in fiber angles were significant in TQ1, TQ2, and TQ4 with fiber angles more positive in HS group. Differences in sheet angles and uniformity index were not significant. Despite having a normal size and shape, we found that hearts in a state of transitional eutrophy have a significantly different fiber and sheet morphology. The experimental data was used to develop a model that represents the path to failure that may be taken by the myolaminae when the heart is subjected to excessive pressure overload
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