Sodium and potassium channel activation time constants

[kew15]

I'm working on a project for a class using Neuron. I'm not very experienced with Neuron, so for the most part, it's an extremely simple model. I have just a single, unmyelinated axon with hodgkin-huxley dynamics. As part of the project, I need to look at conduction velocity and how it changes if the activation and inactivation time constants for the sodium and potassium channels are changed. I know how to measure conduction velocity and everything, but I just need to find out how to alter the values for in/activation time constants for those channels. Are there specific variables that I need to change, or is it something I need to do with NMODL, or what? I'm really at a loss for how to do this.

[ted]

Does your instructor know anything about NEURON?

[kew15]

Yes, but I'm not sure how much he knows. He's never directly taught us anything about it, the only lecture we had where we learned anything about using Neuron was taught by a guest.

[ted]

You can create your own custom version of NEURON's hh mechanism that will give you a new pair of parameters that you can use to change the gna and gk activation gates' rate constants by multiplicative factors.

Start by putting a copy of hh.mod in the same directory as your hoc or ses file(s) for your model axon. If you don't know where to find hh.mod, see http://www.neuron.yale.edu/neuron/stati ... arted.html (if you're using OS X, start looking in the directory where you installed NEURON and drill away with Finder until you locate it).

Rename the copy hhx.mod.

Use a text editor to open hhx.mod and make the following changes:

Change

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TITLE hh.mod   squid sodium, potassium, and leak channels

to

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TITLE hhx.mod   squid sodium, potassium, and leak channels, with adjustable rate scaling

Change

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NEURON {
        SUFFIX hh

to

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NEURON {
        SUFFIX hhx

(because NEURON can't load two mechanisms that have the same SUFFIX)

Now save hhx.mod and check it with modlunit to make sure there are no errors. If you're using Linux, type
modlunit hhx.mod
at the system prompt.
If you're using OS X, drag hhx.mod and drop it onto modlunit.
If you're using MSWin, double click on modlunit (in the NEURON program group in your Start menu), use modlunit's directory browser to navigate to the directory that contains hhx.mod, and when you get there click on its "Selected directory" button.
modlunit should run to completion without reporting any errors. If you see any error messages, locate and fix the errors.

Now you can use mknrndll (or nrnivmodl if you are using Linux) to compile hhx.mod
--see
Q: How do I compile mod files?
in the FAQ list http://www.neuron.yale.edu/neuron/faq/general-questions if you aren't sure how--
and revise your model axon so that it uses the hhx mechanism instead of hh. Make sure your model works properly; it should generate the same results as it did when it used the hh mechanism.

At this point you are ready to add a parameter called mrho to hhx.mod that will allow you to adjust the rate of gna activation. Do this by opening hhx.mod with a text editor, and making the following changes:

Just below the line that begins

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        RANGE gnabar, gkbar . . .

insert this line

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        RANGE mrho : scale factor for gna activation rate constants

Just below the line that begins

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PARAMETER {

insert this line

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        mrho = 1 (1) : use to scale m's rate constants by a multiplicative factor

In PROCEDURE rates make these changes:
Comment out the TABLE statement by changing

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        TABLE minf, mtau, hinf, htau, ninf, ntau DEPEND celsius FROM -100 TO 100 WITH 200

to

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:        TABLE minf, mtau, hinf, htau, ninf, ntau DEPEND celsius FROM -100 TO 100 WITH 200

Change

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        mtau = 1/(q10*sum)

to

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:        mtau = 1/(q10*sum)
        mtau = 1/(q10*sum)/mrho

This means that when mrho is 1, mtau (and the gna activation rates) are unaffected; if mrho is > 1, mtau is smaller which speeds up gna activation, and if mrho is < 1, mtau is larger which slows gna activation.

Save hhx.mod and check it with modlunit. If there are no errors, compile it and run a new simulation. If your model has a section called axon, the hoc name for the mrho parameter in that section will be axon.mrho_hhx, and you will be able to discover the value of mrho by typing

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  axon print mrho_hhx

at the oc> prompt, and assign a value of 2 to it by typing

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  axon mrho_hhx = 2

at the oc> prompt (this particular value of mrho would speed up gna activation in axon by a factor of 2).

mrho_hhx should also automatically appear with the other hhx mechanism parameters (gnabar_hhx, gkbar_hhx, and gleak_hhx) in GUI tools such as ChannelBuilder.

After you have all this running, it will be time to add another parameter called nrho that does the same thing for gk activation. And you'll know how to do it.

[kew15]

Thank you! That is incredibly helpful!

[ted]

Good luck with your assignment.