Compensation for resistance in series with excitable membranes

Extracellular resistance in series (Rs) with excitable membranes can give rise to significant voltage errors that distort the current records in voltage-clamped membranes. Electrical methods for measurement of and compensation for such resistances are described and evaluated. Measurement of Rs by the conventional voltage jump in response to a current step is accurate but the measurement of sine-wave admittance under voltage-clamp conditions is better, having about a fivefold improvement in resolution (+/- 0.1 omega cm2) over the conventional method. Conventional feedback of the membrane current signal to correct the Rs error signal leads to instability of the voltage clamp when approximately two-thirds of the error is corrected. We describe an active electronic bridge circuit that subtracts membrane capacitance from the total membrane current and allows full, yet stable, compensation for the voltage error due to ionic currents. Furthermore, this method provides not only fast and accurate control of the membrane potential in response to a command step, but also fast recovery following an abrupt change in the membrane conductance. Marked changes in the kinetics and amplitude of ionic currents resulting from full compensation for Rs are shown for several typical potential patterns.