Cell receptors
Cell receptors
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Brief story about the cell
Cell
Cell
Cell is the basic structural, functional and biological unit of all known living organisms. Cells are often called the “building blocks of life”. Cell is a smallest unit of life that can replicate independently*. There is a lot of biomolecules such as proteins and nucleic acids in a cell. In comparison with the size of these molecules, the size of a cell is huge.
*There are so much discussions without single solution: can we consider a virus as life? Viruses much less in size than a cell.
*There are so much discussions without single solution: can we consider a virus as life? Viruses much less in size than a cell.
There are so many functional parts inside the cell. For easy understanding you can imagine a cell as giant factory with many plants that manufacture a huge range of biomolecules from very simple things to big protein complexes. As every factory, cell cannot work and live without the roads called cytoskeleton.
Cytoskeleton
Cytoskeleton
Cytoskeleton is a crucial part of a cell with the key functions: to maintain integrity of a cell and to transport biomolecules from one part of a cell to another. There are three types of cytoskeleton structures: microtubules, actin filaments and intermediate filaments.
While cytoskeleton holds parts of a cell separately from each other, cell membrane separates the interior of a cell from outside environment.
While cytoskeleton holds parts of a cell separately from each other, cell membrane separates the interior of a cell from outside environment.
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Image[Import["https://upload.wikimedia.org/wikipedia/commons/0/09/FluorescentCells.jpg"]]
Cells of bull’s pulmonary artery: actine microphilaments colored in red, microtubules colored in green, cell’s nuclei colored in blue.
Cell membrane
Cell membrane
Cell membrane physically separates the interior of all cells from outside environment. This is a strong border with a lot of checkpoints. Membrane represents a bilayer of phospholipid molecules that hydrophobic from one side and hydrophilic from another side. Also, cell membrane contains transport proteins called ion channels and protein complexes called receptors.
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Image[Import["https://upload.wikimedia.org/wikipedia/commons/thumb/7/79/Cell_membrane_drawing-en.svg/1280px-Cell_membrane_drawing-en.svg.png"],ImageSizeLarge]
The cell membrane is selectively permeable and able to regulate what enters and exits the cell. The movement of substances across the membrane can be passive, occurring without the input of cellular energy, or active, requiring the cell to expend energy to transporting it.
To fully describe the main theme of this paper I should disclose the concept of signaling pathways.
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Signaling pathways
Signaling pathway is a cascade of molecules through which the information from cell receptor transmits into the cell. Signaling pathway is a corner stone of the biochemistry of cell. The signal goes from one molecule to another in a strictly defined order that describes the signaling pathway. Much of signaling pathways can be started in answer to extracellular signals such as neurotransmitters, hormones and growth factors. In other cases, signaling pathways start the action prior to intracellular activation. The result of signaling pathway is production new chemical compounds and long-time change of cell’s behavior. As I said before, to start signaling pathway, there is a requirement to have a receptor and the ligand to it.
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What is cell receptor
Cell receptor in most cases is a protein located on the cell’s surface that selectively responds to binding of concrete molecules called ligands. There are many different ligands, but only certain ligands can bind to receptor. Different ligands induces different cellular response. The response may be transcription of a gene, cell growth or many other cellular actions.
Ligand can be a protein or peptide (short protein) or another small molecule such as neurotransmitter (acting in synapses in central nervous system), hormone, pharmaceutical drug, toxin or parts of outside of a virus or microbe.
When ligand connected to receptor, receptor changes own spatial configuration. If the molecule can connect to receptor and start receptor’s function, it called agonist. In case of blocking receptor’s function ligand will be antagonist. Ligands can connect to the receptor in full manner (in this case it is full agonist) or in partial manner (partial agonist). Every receptor can have various ligands dependent on ligand and receptor spatial configuration. This mechanism underlies the action of drugs or poisons.
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Image[Import["https://upload.wikimedia.org/wikipedia/commons/thumb/4/48/Transmembrane_receptor.svg/1280px-Transmembrane_receptor.svg.png"], ImageSizeMedium]
Transmembrane receptor: E=extracellular space; I=intracellular space; P=plasma membrane.
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Image[Import["https://upload.wikimedia.org/wikipedia/commons/thumb/b/be/Membrane_Receptors.svg/1280px-Membrane_Receptors.svg.png"], ImageSizeMedium]
Examples of membrane receptors: 1. Ligands; 2. Receptors; 3. Secondary messengers.
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Receptor types
Transmembrane receptors can be classified by their location:
1. ion channel-linked (ionotropic) receptors;
2. G protein-linked (metabotropic) hormone receptors;
3. enzyme-linked hormone receptors;
1. ion channel-linked (ionotropic) receptors;
2. G protein-linked (metabotropic) hormone receptors;
3. enzyme-linked hormone receptors;
Intracellular receptors found inside the cell include cytoplasmic receptors and nuclear receptors.
Ionotropic receptor
Ionotropic receptor
Ionotropic receptor (IR) is the complex of receptor and ion channel which are linked. Activation of IR opens the ion channel and allows ion transport through channel. Opening the ion channel leads to changing of membrane potential of a cell.
Only concrete ions can pass the channel. Some ion channels only passes one type of ion throughput, another operates in cyclic manner: for example, sodium-potassium pump’s first iteration is transportation 3 sodium ions to extracellular space, and second iteration is transportation of 2 potassium ions to intracellular space. After that, cycle repeats until receptor deactivates.
IR stays activated for a very little time.
Only concrete ions can pass the channel. Some ion channels only passes one type of ion throughput, another operates in cyclic manner: for example, sodium-potassium pump’s first iteration is transportation 3 sodium ions to extracellular space, and second iteration is transportation of 2 potassium ions to intracellular space. After that, cycle repeats until receptor deactivates.
IR stays activated for a very little time.
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Import["http://fulltimebiology.weebly.com/uploads/5/1/6/6/51661907/3273156_orig.gif", "Animation"]
Metabotropic receptor
Metabotropic receptor
Metabotropic receptor (MR) is a receptor that can change the metabolic processes in a cell. MRs have more wide range of functions than IRs. The most common type of MRs is G-protein-coupled receptors, GPCRs. Ligand binding to MR leads to activation of signaling pathway in a cell. MRs stays activated much longer than IRs, up to hours.
Enzyme-linked receptor
Enzyme-linked receptor
Enzyme-linked receptor (ER) also known as catalytic receptor. Ligand binding to ER causes enzymatic activation on intracellular side. Enzymes accelerate chemical reactions.
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Model of neuronal bursting
As I described above, cell functions completely depends on the behavior of various types of receptors. IRs leads to membrane potential change, MRs helps to fit processes in a cell and to adapt a cell for changing of environment conditions, ERs helps to catalyse chemical reactions in a cell.
To observe the results of cell work, I illustrate how activation of many IRs goes to bursting of a single neuron.
Neurons are located in nervous system. Every neuron have connections with thousands other neurons. The connection of 2 neurons called synapse. When membrane potential of neuron exceeds a certain value, neuron spikes. Thanks to rapid activation and deactivation of IRs, membrane potential of neuron can change very fast. It leads to series of spikes that called bursting. After bursting series, neuron can not spike for a time.
In 1984, Hindmarsh and Rose written the paper “A model of neuronal bursting using three coupled first order differential equations” in which show the bursting process in time.
To observe the results of cell work, I illustrate how activation of many IRs goes to bursting of a single neuron.
Neurons are located in nervous system. Every neuron have connections with thousands other neurons. The connection of 2 neurons called synapse. When membrane potential of neuron exceeds a certain value, neuron spikes. Thanks to rapid activation and deactivation of IRs, membrane potential of neuron can change very fast. It leads to series of spikes that called bursting. After bursting series, neuron can not spike for a time.
In 1984, Hindmarsh and Rose written the paper “A model of neuronal bursting using three coupled first order differential equations” in which show the bursting process in time.
This model have 3 first ordered differential equations with 8 parameters.
Equation solving
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diffEq[a_,b_,c_,d_,s_,χ_,r_,i_]:=NDSolveValue[ [t]y[t]-a+b-z[t]+i, [t]c-d-y[t], [t]r(s(x[t]-χ)-z[t]), x[0]0,y[0]0,z[0]0,{x,y,z},{t,0,2000}]
′
x
3
x[t]
2
x[t]
′
y
2
x[t]
′
z
Authors of original paper provided us the values of 8 parameters.
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Manipulate {f,g,h} = diffEq[a,b,c,d,s,χ,r,i]; Column[ Plot[ f[t],{t,700,1500}, ImageSize800, PlotLegends->"Expressions" ], ], {{a,1},1,5}, {{b,3},1,5}, {{c,1},1,10} , {{d,5},1,10}, {{s,4},1,5}, χ,,-3,-0, {{r,0.001},0.0001,0.01}, {{i,2},-10,10}
-8
5
As you can see on plot, after the bursting period membrane potential of neuron drops dramatically and neuron need a relaxation time to restore the potential. Right after potential is restored neuron ready to next spiking series.
This model confirmed of many observations in vivo.
This model confirmed of many observations in vivo.
Further Explorations
Research another neuron models
References:
“A model of neuronal bursting using three coupled first order differential equations” J.L. Hindmarsh, R.M. Rose, Proceedings of the Royal Society of London. Series B, Biological Sciences, Volume 221, Issue 1222 (Mar.22, 1984), 87-102. http://fge.if.usp.br/~reynaldo/verao/hr_3d.pdf
Authorship information
Georgii Galumov
Jun 23, 2017
georgyg2010@gmail.com