RESUMO
A software was designed to simulate the calcium signal following hormone or growth factor stimulation in epithelial cells. The software written in C runs on a PC under Windows environment. It is based on a Markov process where the dynamic of the system is characterised by phenomenological transition probabilities. Moreover a minimal model is proposed to analyse the role of plasma channels and IP3 receptors, together with the opposite action of the CaATPase pumps, in the cytosolic and endoplasmic reticulum (ER) calcium signal control. The simulation is applied on the calcium response following stimulation by carbacol (protein G coupled receptors) or epidermal growth factor (tyrosine kinase type receptors) in A431 epithelial cells. The experimental calcium signals can be grouped in three classes; a spike and a return to the basal level (signal A), a spike and a decrease to a plateau level (signal B) or a slow increase to a plateau (signal C). Epidermal growth factor induces signal A and B while carbacol gives signal B and C. When a 'pseudo' steady state is reached oscillations occur. Computer simulations show that signal A can result from the activation of IP3 receptors while signal C would result from the activation of the plasma channels; signal B appears as the additive contribution of both channels, while oscillations are compatible with a calcium induced calcium release mechanism. Simulations suggest that the calcium dynamic in the ER is a mirror of cytosolic calcium but that a simple way to produce similar calcium elevation in these two compartments is to activate plasma channels. Implications of such a mechanism is discussed.
Assuntos
Cálcio/metabolismo , Simulação por Computador , Proteínas de Ligação ao GTP/metabolismo , Modelos Biológicos , Modelos Químicos , Proteínas Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Algoritmos , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , ATPases Transportadoras de Cálcio/efeitos dos fármacos , ATPases Transportadoras de Cálcio/metabolismo , Carbacol/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Células Epiteliais/metabolismo , Proteínas de Ligação ao GTP/efeitos dos fármacos , Humanos , Processamento de Imagem Assistida por Computador , Fosfatos de Inositol/metabolismo , Bombas de Íon/efeitos dos fármacos , Bombas de Íon/metabolismo , Cadeias de Markov , Proteínas Tirosina Quinases/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptores de Superfície Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Software , Processos Estocásticos , Células Tumorais CultivadasRESUMO
A new approach to study order and disorder in biological membranes and more generally in biological structures is developed. It is based on a graph constructed on the set points representing the position of particles. From this graph, which is called the minimal spanning tree, it is possible to deduce two parameters, namely the average length m and the standard deviation sigma which are characteristic of the repartition to be studied. The use of a diagram involving both m and sigma makes it possible to determine the degree of order by taking a simple reading in the (m, sigma) plane.