www.neuron.yale.edu

Here is an excellent intracellular calcium mechanism in modeldb:

http://senselab.med.yale.edu/senselab/m ... lciumP.mod

My cell model has this internal calcium mechanism in it and some voltage-gated calcium channels (among other things). The internal calcium concentration, cai, spikes up and down along with each action potential (which is mainly driven by sodium activity really, but the calcium concentration kind of spikes in empathy). Cai goes up as calcium comes in with each spike and goes down as calcium is quickly cleared by this mechanism - for instance by the calcium pump it describes. All of the calcium is cleared each spike by this mechanism.

BUT I would like to modify this mechanism to incorporate a degree of calcium accumulation. So that most but NOT ALL of the calcium is cleared each time - a fraction is accumulated each time. And I can control this fraction.

What I hope then is that when we look at the internal calcium plot we see the calcium spikes driven by each action potential - but these spikes get bigger and bigger over time because calcium is accumulating in the cell over time.

BUT my problem is that Im not sure how to do this. I have played with some of the parameters in the mechanism in the hope that I can achieve this result. BUt alas, no. With some changed I can get a growing cai over time - but then the cai does not have spiking in it. So, I have ruined the calcium spiking effect. Which I really wish to maintain. So, I want growing cai, but still with spiking in the cai.

So, what Im wishing for: we see a cai spike, then the next cai spike is a bit bigger, then the next one a bit bigger still, then the next cai spike a little bigger etc. and we go on like this. As everything stands now, all the spikes are the same size. I wish them to gain in amplitude over time. I think a degree of cai accumulation can drive the cai spikes to gain in amplitude.

I would be so, so grateful to anyone that can offer any advice.

Thinking about the problem more I think what I need is an increasing "cainf" over time. After each calcium spike this mechanism brings the calcium level down to "cainf" - the kind of default calcium level. If I can put in some expression that can increase "cainf" over time I think I can get my desired calcium spiking - with the spikes getting larger and larger over time.

My problem is that I'm not sure how to do an expression for cainf increasing over time. I'm currently looking into this. But if anyone knows - a post here would be very gratefully received.

Found in NEURON documentation how to express variables that change with time, t:

BREAKPOINT { i = imax*sin(w*t) }

So, now applyin this to my situation (based on y=mx+c):

BREAKPOINT { cainf = (0.000001*t) + 2.4e-4 }

And so now we do see cainf increase with time. Brilliant! And this does cause the calcium spikes to increase in size over time. Brilliant!

A problem is that I dont have calcium spiking all the time in the cell model. And with this method cainf is still increasing in value when there is no calcium spiking. A big flaw. When there is no calcium spiking I dont want the cainf to rise in value. In fact it would be nice if it could drift back to a set value. But I think now I am really out of my depth as I have no idea how to get this.

Actually. I think I know what I am doing on this now. I have a remaining issue on communication between .mod mechanisms. But this perhaps warrents its own thread. So, I will set up another one.

Well I am looking for some help for my project work that is based on the role of the calcium in human brain functions, frankly speaking I did not get the basics right when the thing was explained in our class, so can someone help me here? Have to finish the project in a short time and am at sea as to how I complete this before the deadline.