Model of NK1 receptor action

[pauloaguiar]

I want to model a NK1 receptor (target of the neuropeptide SP). Little is know about the mechanism of this receptor but people are convinced that one the main results of its activation is an increase of intracellular calcium concentration (Ca is released from intracellular buffers, eg ER).
I use a detailed mod for intracellular calcium dynamics (buffering, pump and diffusion) which naturally has a "USEION ca ... WRITE cai". Now, the question is, what is the correct way of changing cai from my NK1R mod file. Notice that NK1 is not creating a "ica"; it is directly affecting "cai".

Thanks in advance for your attention!

Paulo

[ted]

The "best" answer depends on your conceptual model of the effect of SP on cai.
What time course do you want SP concentration to follow?
Can you provide a mathematical statement of the relationship between SP concentration
and cai?

[pauloaguiar]

Hi Ted,

first of all, thanks for your fast reply!

The key assumptions in my NK1R mod are (*):
1) the activation is performed using a NET_RECEIVE block; SP is (typically) co-released with glu so, my idea is to use this receptor together with AMPA and NMDA (i.e. the pre-synaptic compartment sends an event to all three receptors)
2) once activated, the NK1R does not activate any channel (or currents); instead, it gives rise to a cascade of events that ultimately leads to release of calcium from intracellular buffers; (as you may suspect, in the model I'm working on, I have [Ca]i dependent currents...)
3) calcium buffer release follows a dual-exponential profile (tau_rise, tau_decay) and is subject to an intracellular calcium concentration dynamics (coded in an independent mod)

Now, back to "the problem": I have two mods that WRITE cai.
I can't merge the two mods into one and I can't model NK1R with WRITE ica since it is not generating transmembrane ica currents.


ps:: (*) Yes, this is a very simplistic view of NK1R action, I know. But, as you may suspect, in the model I'm working on, I have [Ca]i dependent currents and even this simple mod may shed some light to the contribution of SP to the neuron firing dynamics.

[ted]

In order to suggest the best strategy for doing what you want, we will need to get into a
level of discussion that is probably best served by direct email communication. Can you
send me
ted dot carnevale at yale dot edu
the mod files you're working with, as well as a concise summary of the
equations and/or kinetic scheme that expresses the conceptual model that you want to
implement (or a citation of an article that presents such a summary)?

[pauloaguiar]

Thanks Ted, I'll send the email and files right away.