Dear community:
I would like to seek opinions from you on current-clamp mode in electrophysiology. I am trying to record voltage response from neurons, so I first do whole-cell recordings on the neurons and then use the current clamp mode provided by the amplifier (Axon Multiclamp 700B).
If my basic knowledge on electrophysiology is correct, then doing whole-cell recording basically "open a hole" on the cell membrane. This may effectively change the electrical structure of the cell, and cause distortion of voltage signals sensed by electrode. In particular, I wonder if whole-cell recording by itself will decrease the input resistance of the cell, so the current will "leak out" from the hole we make on the membrane, instead of charging the membrane. This problem, if true, will be particularly bad for me, because the neurons I am interested are peripheral sensory neurons, and are small (soma
The "hole" isn't to the extracellular space but to the interior of your recording pipette, which in turn is attached to a high input impedance amplifier. There are some electrical concerns related to the series resistance and pipette capacitance -- see the nice exposition by Boris Barbour (https://www.ibens.bio.ens.psl.eu/spip.php?article296&lang=fr) -- but these concerns are different than the concern you raise.
Though, one other thing you might worry about (sorry) is that the volume of fluid in your patch pipette is vast compared to the volume of the interior of the cell. So, soon after achieving whole cell mode, you're dialyzing the cell rather effectively. That can be a problem depending on what you're trying to measure. If that is the case, you might try a peforated patch recording rather than whole cell.
As Niraj already wrote, the 'hole' is not to the extracellular space and, thus, is not a problem. Be sure to compensate for series resistance. I can recommend 'The Axon Guide'.
Leak currents from 'bad' patches might be a bigger problem in your case.
As an addendum to the previous answers, I would point out that the sole path for current flow to the extracellular solution is around the pipette tip. You can evaluate the relevance of this pathway by measuring seal resistance in cell-attached mode, that is, before getting the whole-cell configuration.
Albertino
Thanks for all the response above. I also realized that the hole opened by the pipette does not connect to the ground electrode so it cannot form a closed loop except by charging the glass pipette, which can be cancelled by capacitance compensation. Also, even if compensation is not done properly, this charging will only affect some kind of time constants.
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