(A) Physically, membrane capacitance varies with surface area, thickness and lipid composition (B) Virtual capacitance modification via the CapClamp is a form of dynamic clamp, a fast feedback loop between intracellular voltage sampling and computer-controlled current injection: given the measured cell capacitance , the target capacitance , recorded membrane potentials and the sampling interval , the computer calculates clamping currents required to mimic the desired change of capacitance (see Equation 1). (C) Clamping a hardware-implemented model cell (RC circuit) at a decreased (left) or increased (right) capacitance leads to faster respectively slower charging of the ‘membrane potential’ to the same steady-state voltage response (top row, black: recordings, dashed red and blue: exponential fits , gray: recording at original ) in response to a step current (2nd row) due to the clamping currents (3rd row). As a result, the current through the resistance (4th row) has a different profile and the apparently deposited charge (bottom row, black) by the ‘cellular’ transmembrane currents decreases, respectively, increases as expected for a capacitance change. The real deposited charge (bottom row, gray), taking into account the clamping currents, has the same steady-state amplitude in all three cases, because the physical capacitance did not change. (D) Measured time constant , voltage responses , resistance , deposited charge (apparent and total) and capacitance versus target capacitances.