Dear R. Norman:
Once again, thank you very much for your nice explanations. As I
understand of your comments, it is always desirable to acquire currents
better than potentials when studying synaptic responses (i.e to
Glutamate, GABA or ACh among others...). Is this issue only due to
technical limitations?. For example, intracellular recordings provide a
big leak current, and that's the reason the people only record
potentials. Field potentials represent a population of cells, and this
is not suitable to study single responses....
Anyway, even under path-clamp conditions you wrote that unless we
suffice the space-clamp conditions, or have a patch of membrane, is
impossible to study the conductance. If we discard these two issues, is
always desirable to acquire PSC better than PSP?
The question is that I don't understand why is better to record current
responses in stead of voltage responses. (i.e we could study AMPA/NMDA
component of potential....).
As you can see, I'm just starting in this exciting field, and I am quite
new. A little bit of would be really of guide would be very appreciable!
On the other hand, would you be so nice to tell where I can access the
papers of Hodgkin and Katz 1949, the Hille book (my bedside book) only
refers the experiments... and a more detailed experimental approach
would be very interesting for me.
Thanks you very much in advance for your time!
r norman wrote:
> On Wed, 22 Feb 2006 19:29:36 +0100, SJM Guzman
> <jose.guzman at medizin-uni-leipzig.de> wrote:
>>>>Hi R. Norman:
>>>>Your explanation was fabulous. I was kind of confuse regarding the
>>terminology homosynaptic/monosynpatic. Now is clear to me. Again thank
>>you very much.
>>>>Regarding the field potential question.... To access the monosynaptic
>>component, some laboratories analyze EPSP slopes using the least-squares
>>regression. Why not simply to analyze the amplitude?
>>>>Here some examples of publications...
>>>>"For EPSP analysis, The initial rising slope was measured, (1 msec
>>period form its onset, in milivolts per millisencond), which contains
>>only a monosynaptic component )..."
>>>>"To minimize the contribution of voltage-dependent conductances, initial
>>slopes of EPSPs were calculated..."
>>>>I would appreciate some literature about it. I miss some about PSC/Ps,
>>because traditional electrophysiological books (i.e Hille, Neher &
>>Sakmann), don't tell much about it.
>>>>Thank you very much again!
>>> It is very easy to find a lot of papers that refer to PSP slopes,
> whether measured as field potentials or with intracellular electrodes.
> However I have not been able to find any web sites that explain just
> why this measurement is used.
>> Here is my interpretation, but this is really conjecture on my part.
> Somebody jump in here if it is wrong!
>> The really proper direct measure of synaptic response is channel
> opening. However that can't be seen directly. Channel opening is
> directly related to membrane conductance. However measuring
> conductance is often technically impossible, is disruptive to normal
> cell function, and averages conductance changes over too large an area
> of membrane. The next most direct response is synaptic current. If
> the membrane is voltage clamped to a fixed value, the current through
> any one synapse will be directly proportional to the channel openings
> (conductance changes) assuming the reversal potential (ion
> concentrations) do not change significantly. The most indirect
> response is synaptic potential itself. The amplitude of the psp will
> depend greatly on all sorts of disturbing influences going on in the
>> So measuring synaptic current is a far better way of measuring
> synaptic function than measuring synaptic potential. Unfortunately,
> directly measuring current usually means doing a voltage clamp which
> is often technically impossible. However, the slope of the rising
> phase of the psp is a very good measure of synaptic current. During
> this time, the current through the synaptic channels completes its
> closed loop by flowing across the membrane in the form of capacitative
> current which obeys the law I = C dV/dt. Since C is essentially
> constant, dV/dt is a direct measure of I. The falling slope is very
> different since the synaptic channels are then closed and that slope
> depends on the cable properties of the cell, especially the way that
> the current distributes longitudinally down the dendrites and the
> membrane time constant. Note: the "effective time constant" during
> the rising phase of the psp is very different from that during the
> falling phase because of the changes in membrane conductance.
>> I don't know just where all this is explained. I do know that Hodgkin
> and Katz (I think it was their 1949 paper, I don't have my texts with
> me on vacation) used the slope of the rising phase of the action
> potential as a far better measurement of the sodium current inrush
> than the actual amplitude of the action potential. They explained why
> in an appendix to the paper. Just as the action potential is caused
> by sodium currents flowing through open sodium channels, the synaptic
> potential is caused by ion currents flowing through open synaptic
> channels and the same logic applies.
>> If I recall correctly (again, I don't have the books with me) Neher
> and Sakmann concentrate (as to be expected) on patch clamp data and I
> seem to recall Hille doing similarly. Many texts go into the
> molecular machinery of ion channels and receptor binding and so on but
> short change the biophysics of the electrical details.