Drift in Resting Membrane Potential for Coupled Cells

[shailesh]

Here is the scenario:
> Three cells (A,B,C) coupled via gap junctions forming a chain:
A ----- B ----- C
> All cells have been assigned identical biophysical parameters. They are equipped with some custom active channels.
> When isolated (i.e. no gap juntions), each cell has a resting potential of -69mV.
> But when the gap junctions are set, the resting membrane potential initially shows a series of AP like bursts and then slowly drifts to -40mV - v_init is set to -69mV at the start of this simulation; i.e. the resting potential of the isolated cells
> If I run the above simulation with v_init = -40mV, then I see some smaller and shorter activity and it settles down at -40mV.

My Question:
1> How does the system of 3-coupled identical cells have a different resting potential than the isolated cells?
2> On tracking the Vm of each cell for the initial time steps, I find that the terminal cells tend to depolarize spontaneously (very minutely) as compared to the central cell, thus causing an inward gap junctional current into the central cell. What causes this depolarization of the terminal nodes? Where/how does the potential gradient arise between the cells?

My only lead currently is that cells A and C, the terminal cells, have a higher input resistance (as just one gap junctional pathway) as compared to cell B, the central cell with two gap junctional pathways. But not sure how to correlate this with the above observation.

I tried investigating the gap junctional current, but it seems to have a +/- alternating direction with decreasing magnitude, as the cell approaches the eventual resting potential of -40mV. I tried adding extracellular mechanism to plot the membrane current, but it too had a similar current plot.

[ted]

Strange stuff. Without being able to reproduce the phenomena, I can only offer empty speculation. If you want me to say anything substantive about it, please zip up just enough code to reproduce it and email to ted dot carnevale at yale dot edu