Leak Subtraction
At this point we can also usefully discuss the leakage current control, which performs a complementary action in voltage clamp mode, and works in a similar way. The problem in this case is that there may be leakage pathways that effectively appear between the headstage and ground. In true patch recording mode, an imperfect seal of the patch electrode against the cell membrane results in a leakage current pathway through the seal to the external solution, which is at ground potential or effectively so. A similar leakage pathway can also be present in whole cell recording mode, of course, but in this case there may be a membrane leakage conductance as well, which appears in parallel with the patch seal leakage. Unlike the effects of the access resistance, such leakage pathways will not affect the accuracy of the voltage clamping (except insofar as they may worsen the errors due to the access resistance if the leakage current is high). The primary effect of a leakage pathway is that a component of the total current will flow through it, in proportion to the potential difference across it, so this can be corrected by subtracting an appropriate proportion of the command voltage from the current signal.
Although the leakage pathways are also present in current clamp mode, trying to compensate for them in this case serves no useful purpose, as their only effect is to take a constant proportion of the current. This effect is easily corrected if required by applying a proportionately larger current. In contrast, leak subtraction of the current record in voltage clamp mode IS useful, because it changes the overall form of the record by affecting just one component of it. It is therefore most appropriate that leak subtraction is provided in voltage clamp mode only, as we have done here.
As we shall see again later on, it is often more convenient to deal in units
of conductance rather than resistance, and that is the case here because the
leakage current control follows a conductance rather than a resistance law. It
is a calibrated ten-turn potentiometer, and the minimum setting corresponds to
zero conductance (i.e. zero leakage current). The maximum setting corresponds
to 1 nanosiemen conductance (1 gigohm resistance) in the patch and small cell
modes, and 100 Nanosiemens (10 Megohms) in the big cell mode. The associated
on/off switch allows this control to be inactivated if required.
