Reference Section • 129
Chapter 5
The tendency to oscillate therefore depends on the relative magnitude of the
electrode resistance to the electrode capacitance and the degree of
compensation of the electrode capacitance. Thus, one should take care that C
m
is well compensated as one advances correction. In addition, the tendency to
oscillate can be reduced by limiting the bandwidth of the positive-feedback
circuit. This is the function of the Bandwidth control.
Limitations of R
s
Compensation
Series-resistance compensation is an attempt to electronically reduce the effect
of the electrode resistance. Because of practical limitations, it is never perfect.
Even if 100% compensation could be used with stability, this would only
apply to DC and medium-speed currents. Very fast currents cannot be fully
corrected.
For best results, the cell membrane resistance should be many-fold higher than
the electrode resistance. This is normally the case for cells at rest containing
small drug-activated or synaptic currents. However, during voltage activation
the cell membrane resistance could fall a hundredfold or more to values similar
to or less than the series resistance. In these cases it is probable that:
1. There will be a significant error due to the voltage drop across the
electrode. This error is not obvious to the user because the patch clamp
controls the combined voltage drop across the electrode and the cell.
2. The setting of the Whole Cell compensation controls will become
erroneous because it is based on the time constant to charge the membrane
capacitance before the change in membrane resistance occurred. Since this
time constant depends on the parallel value of membrane resistance and
the electrode series resistance, this error could become substantial.
If the cell input resistance becomes comparable to, or less than, the electrode
resistance, the whole-cell patch clamp technique will probably not work. In
this situation it would be preferable to use a discontinuous (chopped) single-
electrode voltage clamp, such as the Axoclamp.
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