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 ofthe most versatile and ubiquitous intracellular messengers since it is able to regulatediverse number of functions such as proliferation, secretion, fertilization, metabolism,learning and memory. In the last couple of years, evidence has been accumulatingthat Ca2+ ion is able to integrate information from multiple signaling pathways andconvert this information into a code which regulates events ranging from contractionto modification of gene expression (Berridge et al. 1998). It was shown that Ca2+concentration displays oscillatory behavior in response to agonist stimulation in avariety of cells(Goldbeter 1996) and the frequency of these oscillations increases withthe concentration of agonist, a behavior called frequency encoding which has led to theconcept that many Ca2+-regulated processes are controlled by these codes(Berridge1998).Although the presence of Ca2+ oscillations and the sources of Ca2+ pools involvedis known in many cell types, it is yet not known how the various frequencies ofCa2+ oscillations are converted into codes that regulate the numerous cellular events.Recently a number of cellular targets that decode Ca2+ signals and are tuned tothe 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 oxytocinand vasopressin-induced Ca2+ oscillations in cells of normal rat liver (Clone 9) andcells of pregnant human myometrium. The proposed model accounts for the receptor-controlledCa2+ oscillations involving positive feedback leading to activation of phospholipaseC (PLC) and negative feedback from PKC onto G-proteins which simulatesmany of the features of observed intracellular Ca2+. The model also incorporatesthe concept that coordinated Ca2+ signals in a group of hepatocytes require botheffective gap junctions and the presence of agonist at each cell surface. Another objectiveof this research is to understand the relevance of frequency-encoded signalsby performing an analysis of frequencies of Ca2+ oscillations using the Fast FourierTransform and the Wavelet Transform. The validity of the model was confirmed byusing statistical tests to check if the frequencies and amplitudes of the experimentalCa2+ oscillations match with those of the modelled oscillations.
展开▼
