Flash link: https://vlab.amrita.edu/repo/BIOTECH/NEO/Neuron_simulator/Neuron_Sim3.swf
General procedure
Neuron Simulator is an online simulating platform for a section of excitable neuronal membrane of squid axon. Simulator uses Hodgkin and Huxley equation and provides full accesses to HH parameters, membrane parameters, various ionic concentrations, pharmacological effects, stimulus parameters and Vclamp protocol. Loading Neuron simulator by clicking on the tab called “simulator” (see the below sample screen shot of the simulator).
The simulator consists of two main sections: simulator window and variables menu. The simulator window shows the membrane potential plot and plots of various parameters. The upper plot shows the membrane potential vs. time plots (red), stimuli just below the Vm(blue) and lower plot displays a variety of parameters including HH-parameters, various currents and conductance any three variables at a time can be plotted in this window, by default I_leak,Ina,IK was plotted.
Click on the Stim1/Stim2 buttons to inject depolarization / hyperpolarization current to neuronal membrane. Simulation parameters can be modified in Membrane window, Channels window, Drugs window, Stimuli windows (see the figure below).
Simulation control window
Simulation control menu is used to simulate the experiments. The functionalities includes, Run button (will continuously simulate the neuronal membrane, without giving any input stimuli), Stop button (will help to stop the stimuli at any point of time), Stim1 and Stim2 buttons (are two are used to inject an external stimulus as some nA of current to the neuronal membrane, user can modify this by clicking Stim1 and 2 window). Simulation runs for around 30ms when a stimulus (Stim1/Stim2) is applied, Export button (this functionality of this simulator will give user to the freedom of accessing/exporting the simulated models data to an excel sheet, by using these data user can make high resolution pictures) and finally the Reset button (helps to reset the whole simulator).
Membrane window
Membrane window provides accesses to internal and external ionic concentration and membrane properties.
Channel window
Channel window provides accesses to various parameters of passive as well as active channel types. Individual channel can be disabled by making the conductance of that channel to zero.
Passive channels conductance can be varied in the channel window. Voltage gated channels parameters can be accessed by clicking on channel details. Channel details will display a new detailed window with channel properties of fast sodium, delayed rectifier, user defined channels. The figure given below shows the detailed channel properties of fast sodium channel.
Stimuli window
Stimuli window consists of two external stimuli (Stim1 and Stim2) which can be set by user, each of which consists of either single pulse or a sequence of two independent adjustable pulses.
Drug window
Drug window allows to study the pharmacological effect in neuronal membrane by the application of three drugs TTX (Inhibit Na current), TEX (Inhibit K current), Pronase (eliminate Na+ inactivation).At any point of time these drugs can be applied.
Procedure for Resting membrane potential experiments
In this exercise we will be studying resting ion channels and its importance in maintaining resting membrane potential and the equilibrium potential of a cell with a single channel type.
While simulating all the experiment in this exercise please note that, voltage gated channels are off (by changing its conductance to zero, in channels > channel details > sub window [see the figure below]) only three passive channel are functional.
Here we are plotting I_leak, the leakage current, rest all parameters in the bottom graph make it unmarked. I_leak is equal to the flow of current through the passive channels, and its scale is in -0.05 pA to 0.05 pA.
These above changes reflect in the resting membrane potential to a new level -50 mV, to measure exact value for resting potential one can move the mouse pointer over the plot. At normal / the neuronal membrane potential is at rest, some voltage gated channels and leakage channels where opened. When voltage gated channels where closed/disabled, only the leakage channels are open and as a result the resting membrane voltage rises. After any change in membrane property variables, we should run the simulator for some millisecond to reflect the changes in the variables (see general procedure 1.1).
Internal and external concentration of ions (Na+,K+,Cl-) can be manipulate in the membrane window(see the above figure, left red box). Nernst equation for equilibrium potential for individual ion channel is implemented in this window (see the above figure, right red box). User can accesses other membrane properties such as capacitance, resistance and temperature (see the above figure, bottom red box).
Hit the reset button at the right corner of the simulation control window, to reset all parameters to its initial/default values.While simulating all the experiment in this exercise please NOTE that, voltage gated channels are off (by changing its conductance to zero, in channels details sub window).
Help:
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Neuron Simulator is based on David S. Touretzky's Hodgkin-Huxley Simulator.
