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 provides accesses to internal and external ionic concentration and membrane properties.
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 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 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 Modeling the sodium ion channel and its effects on neural signaling experiments
In this exercise we are studying the importance of Na+ channel in action potential initiation and understanding the dynamics of Na+ channels in detail.Na+ channel consists of activation and inactivation gates, both these gates regulate the ionic movement across the membrane. The activation gate described by m3 and inactivation gate described by h. We will explore m,h,gNa dynamics in this exercise, mark m,h,gNa in bottom plot, gNa is plotting in 0-30pS scale.
Press Stim1/ Stim2 (with default stimuli) to simulate the neuronal membrane and inject current to generate spike. By marking the variables m,h and n in bottom plot are the HH parameters varies between 0 and 1. Recall from the theory that fast sodium channel dynamics is proportional to m3h and potassium channel dynamics proportional to n4.
Neuronal membrane is at resting potential the sodium conductance will be at zero, because the activation variable m closes to zero and inactivation variable rest around 0.5(see the above figure) . When a stimuli (Stim1 / Stim2) depolarize the neuronal membrane the Na+ activation gate m opens, the conductance of sodium increases and the membrane depolarizes (see the above figure). As a result membrane voltage level increases, inactivation gate (h) remains close a while (activation gate m remains open) (see the above figure).
Opening of K+ channels cause repolarization of the membrane (without these channels the membrane remains depolarize) this we can simulate by changing the conductance of K+ channels to zero. After the above changes apply Stim1, the neuronal membrane will depolarize but not repolarize because of absent of K+ channels, the Vm remains high (see the above figure). Note that the spike peak is around 50mV without active K+ channels, the cell repolarize the Vm decline from the peak, measure the new resting value. The new resting value is contributed by leakage channels and (not fully closed Na+ channels).
Voltage gated channel parameters
The dynamics of voltage gated channels are described by activation variable (m) and inactivation variable (h) based on membrane voltage. The parameter m is the probability that the activation gate to be open (m3). The parameters including the maximum conductance of Na+ channel can be accessed in a sub-window called m-window in the channel details of fast sodium channels (see the figure below). n sub-window inside the channel details of fast sodium channels (see the figure below) describes the inactivation gate.
The dynamics of activation governed by two rate variables, 1) α (alpha) is the rate at which the channel closed to open and β (beta) is the rate at which the channel open to close. ) α and β are determined by exponential function, user have the ability to choose different exponential function which already defined or user can define its own function to simulate (see the figure below, right side red box).
The user has the accesses to various parameters (like Magnitude, Threshold and Slope) of α and β channel states (see the figure above, left side red box). The inactivation gate described in n sub-window, user has the accesses to various parameters of α and β rate variables.
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Neuron Simulator is based on David S. Touretzky's Hodgkin-Huxley Simulator.