In my data set, I am seeing exposure to my peptide of interest leads to significant increases in action potential firing responses.
But in the same cell types, I am seeing a decrease in the membrane time constant after fitting I-V responses to a standard exponential function.
Does this make sense?
Hi Cody
Maybe I do not understand your question correctly; but I would find it natural that a smaller time constant is associated with increased excitability/action potential firing, because the decrease in membrane time constant could reflect a decrease in membrane capacitance. This would mean excitatory currents would more readily affect a voltage depolarisation and bring the neuron toward firing threshold.
You should be able to easily analyse membrane resistance as well as capacitance from your test pulses, to indeed confirm which of these are involved in the time constant change.
Does this help you?
All the best
Jan
Hi Cody,
Answer is Yes.
It depends in the conditions and timing in which you measure you membrane time constant. If the peptide induces an increase in open probability of a ionic channel, resistance comes down, and time constant comes down. So experimentally you would see a reduction in time constant, this is what it would be expected.
Regards
Enrique
Hi Cody,
I would suggest to have a look at your cells' membrane resistance for an easier interpretation of the observed changes. Remember the relationship between time constant, resistance and capacitance: tau = RC.
In conditions where membrane resistance does not change, a change in the time constant would indicate a corresponding change in the membrane capacitance, so that the ratio of tau/C stays constant.
In your case, you have a change in membrane excitability accompanied by a change in the measured time constant. If your recordings are healthy and stable, and you did not observe any changes in the access resistance, the most probable cause of changes in the time constant is a change in membrane resistance.
However, remember that in order to properly measure all those parameters you need to evoke small voltage changes which do not activate any voltage-dependent currents.
Have a nice weekend!
Marcin
Sure, both a decrease in time constant and an increase in excitability might happen together And one reason is that the ion channels controlling the one might be different than those controlling the other.
Time constant: I assume you are measuring the membrane time constant near the neuron’s resting potential. Consider a typical cortical neuron. Near rest (say, Vm around -65 mV), the active channels might include some mix of leak (voltage-independent), HCN (which produces a hyperpolarization-activated current), and GIRK (inwardly-rectifying potassium). If your peptide increased the conductance of any of these, that might show up as a decrease in resting input resistance and hence a decrease in time constant.
Excitability: But excitability might involve a wholly different set of channels. It depends on what exactly you mean by “excitability” and how you’re measuring it. If you’re injecting current steps and counting action potentials or constructing f-I curves, then among the channels that would be important are sodium (of course), SK and BK (calcium-activated potassium), A-type and D-type (potassium), some flavor of calcium, and others. And for some cell types, these conductances won’t be really be active at rest and won’t show up in a measurement of membrane time constant.
So, to decide if your results make sense, you have to concentrate on how you’re measuring these things. Measuring something when a neuron is just sitting near its resting potential is very different than measuring something when the neuron is depolarized and spiking.
Also, I would mostly focus on ion channels, not capacitance. Unless you think your peptide is significantly altering neuronal morphology, ion channels are the better bet. It's true that dendritic spines and filopodia are dynamic, but in a somatic recording (which is what I assume you're doing) that kind of thing is hard to pick out.
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