HCN channels modulation by cAMP

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HCN channels modulation by cAMP

Postby mart » Wed Mar 01, 2017 7:01 am

Dear modelers,

I am very interested in having the (deterministic) HCN channels of my neruon modulated by [cAMP] however, I didn't find lots of information about this topic. To my knowledge, the only related post in this forum is this -https://www.neuron.yale.edu/phpBB/viewtopic.php?f=18&t=3025-, and it didn't generate that much participation. I understand that the first step is to obtain a mathematical description of the phenomenon. After reading this paper -http://www.nature.com/nature/journal/v411/n6839/abs/411805a0.html- I understood that -probably- the most interesting process to be captured in mathematical equations is the dependency on [cAMP] of the V_1/2 (half-activation voltage) of the Ih mechanism. I didn't find any satisfactory way for obtaining such equations (the only math present in the paper is mostly structural modeling of molecules).

Am I wrong? Perhaps the mentioned modulatory process has already been modelled and I missed it?
If not, I think that the modelers community could benefit a lot from a first NEURON(R) implementation of this modulation.
I am willing to start struggling with it:
Can anybody provide me with some primary material?

Best wishes,
mart
mart
 
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Re: HCN channels modulation by cAMP

Postby ted » Wed Mar 01, 2017 11:04 am

There has been a lot of work on these currents over many years, most of it well above the molecular level. It would be very surprising if there were not already at least one paper that presents a model for the cAMP dependence of h currents. Indeed, a preliminary search of the Internet for
hcn camp dependence model
quickly turns up this paper from Siegelbaum's lab

Activity-dependent regulation of HCN pacemaker channels by cyclic AMP: signaling through dynamic allosteric coupling.
Wang J, Chen S, Nolan MF, Siegelbaum SA.
Neuron. 2002 Oct 24;36(3):451-61.
PMID: 12408847

which presents such a model. The vintage of this publication suggests that there are many more yet to be found; it would probably be more fruitful to do such searches with PubMed.

A search of ModelDB https://senselab.med.yale.edu/ModelDB for entries that involve h currents finds 219 models, each of which includes its source code. Indeed, one of those entries (19176) is a NEURON implementation of the model described by Wang et al.. You might want to examine the others to see if any explicitly represents cAMP effects.
ted
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Re: HCN channels modulation by cAMP

Postby mart » Wed Mar 01, 2017 11:22 am

Ok, thanks.
I clearly haven't looked carefully enough.
I will come back with more specific doubts after having a look to the references you mentioned.

Sorry for the inconvenience.
mart
 
Posts: 13
Joined: Tue May 06, 2014 11:59 am
Location: Physiology Department - University of Bern

Re: HCN channels modulation by cAMP

Postby ted » Wed Mar 01, 2017 11:39 pm

No need to apologize at all. The web is full of information, but the question is often: where to start looking for what particular kind of information? Figuring that h channels have been the target of scrutiny for 4 decades or so, it seemed a pretty sure bet that a google search would turn up something of interest. That said, when it comes to finding published model implementations that are relevant to neuroscience, there's really only one place to look: ModelDB. And of course PubMed is a great tool for targeted literature searches.

But there's at least one more place to look: BioModels database https://www.ebi.ac.uk/biomodels-main/. After all, h channels aren't just found in neurons. Much of the h channel literature is on cardiac muscle. BioModels database is much less neuro-centric than ModelDB, so it's likely to contain interesting models of h currents from all kinds of cells.
ted
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