Team:Valencia/Modelling

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== '''Modelling''' ==
== '''Modelling''' ==
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Our aim in this part of the Project is the development of a model which describes how intracellular calcium concentration changes in time when we apply electrical stimulation, this is, a potential difference across the plasma membrane. We have considered very interesting to make different approaches to this problem: on the one hand, a deterministic model of the calcium influx through the voltage-dependent calcium channels (VDCCs) of excitable cells (neurons and muscle cells) and yeasts -based on the Hodgkin-Huxley model modified by Yamada et al [ISBN:0262111330]-, and, on the other hand, we have included stochastic methods for a further study of these gates, particularly of its activation/inactivation. We are working hard to offer you this model in an easy and clear way, also trying to allow you to interact with the system.
Our aim in this part of the Project is the development of a model which describes how intracellular calcium concentration changes in time when we apply electrical stimulation, this is, a potential difference across the plasma membrane. We have considered very interesting to make different approaches to this problem: on the one hand, a deterministic model of the calcium influx through the voltage-dependent calcium channels (VDCCs) of excitable cells (neurons and muscle cells) and yeasts -based on the Hodgkin-Huxley model modified by Yamada et al [ISBN:0262111330]-, and, on the other hand, we have included stochastic methods for a further study of these gates, particularly of its activation/inactivation. We are working hard to offer you this model in an easy and clear way, also trying to allow you to interact with the system.
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<b>Voltage-gated calcium channels</b> were first identified by Fatt and Katz (1953) [PMC1366030] in crustacean muscle. Then it was discovered that there are different channel subtypes in excitable cells and, some years later, it was accepted that there are analog calcium channels in yeast plasma membrane.
<b>Voltage-gated calcium channels</b> were first identified by Fatt and Katz (1953) [PMC1366030] in crustacean muscle. Then it was discovered that there are different channel subtypes in excitable cells and, some years later, it was accepted that there are analog calcium channels in yeast plasma membrane.
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*'''Modelling Ionic Current Flow through VDCCs'''<br>
*'''Modelling Ionic Current Flow through VDCCs'''<br>
If we assume that the whole calcium currents occur through this calcium channels and that the instantaneous current-voltage relation is linear, we can describe the ionic current <i>I<sub>Ca</sub></i> by the Ohm's law:<br>
If we assume that the whole calcium currents occur through this calcium channels and that the instantaneous current-voltage relation is linear, we can describe the ionic current <i>I<sub>Ca</sub></i> by the Ohm's law:<br>
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We have neglected the intracellular diffusion of calcium due to the different concentrations between the inner perimembranal area and deeper areas of the citoplasm, we have considered that the calcium release from intracellular organelles (for instance, endoplasmic reticulum and mitochondria) may reduce these concentration differences. Thus, we assume the calcium concentration just below the plasma membrane as whole intracellular calcium.
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We have neglected the intracellular diffusion of calcium due to the different concentrations between the inner perimembranal area and deeper areas of the citoplasm, we have considered that the calcium release from intracellular organelles (for instance, endoplasmic reticulum and mitochondria) may reduce these concentration differences. Thus, we assume the calcium concentration just below the plasma membrane as whole intracellular calcium.-->
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Some recommended bibliography for this part of the project can be consulted [https://2009.igem.org/Team:Valencia/modellingbiblio here]
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Latest revision as of 22:49, 21 October 2009



Modelling


Our aim in this part of the Project is the development of a model which describes how intracellular calcium concentration changes in time when we apply electrical stimulation, this is, a potential difference across the plasma membrane. We have considered very interesting to make different approaches to this problem: on the one hand, a deterministic model of the calcium influx through the voltage-dependent calcium channels (VDCCs) of excitable cells (neurons and muscle cells) and yeasts -based on the Hodgkin-Huxley model modified by Yamada et al [ISBN:0262111330]-, and, on the other hand, we have included stochastic methods for a further study of these gates, particularly of its activation/inactivation. We are working hard to offer you this model in an easy and clear way, also trying to allow you to interact with the system.

  • What are VDCCs?

Living cells are surrounded by semipermeable membranes containing specialized proteins providing for exchange of various atoms and molecules between extracellular and intracellular spaces. Two basic mechanisms of transmembrane transport have been recognized: carriers and channels.

V VDCCs.gif

Carriers, such as the Ca2+ pump, Na+-Ca2+ exchanger, or Na+-K+ pump, transport ions against concentration and/or electrical gradients are coupled to metabolic energy consumption. Membrane channels are viewed as pores, which, when opened, allow passive transport downhill the electric and/or concentration gradients. Opening of a channel can be accomplished in two ways:

  1. by binding of a specific ligand either directly to the channel or to another membrane protein coupled to the channel
  2. by a change in transmembrane voltage.

The first pathway is characteristic for ligand-gated channels, such as the glutamate or acetylcholine receptors. The second pathway activates the so-called voltage-gated channels. The foundation of biophysical analyses of voltage-gated ion channels was laid in the pioneering works of Hodgkin and Huxley in the 1930s and culminated in the 1950s by formulating the Hodgkin-Huxley model of action potential (Hodgkin and Huxley, 1952 [PMC1392413]).
Voltage-gated calcium channels were first identified by Fatt and Katz (1953) [PMC1366030] in crustacean muscle. Then it was discovered that there are different channel subtypes in excitable cells and, some years later, it was accepted that there are analog calcium channels in yeast plasma membrane.

Some recommended bibliography for this part of the project can be consulted here

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