(A) (a) In experiments from Smirnov et al. [10], bath application of quinine blunts the GABAA-mediated depolarizing response (top panels show membrane potential measured in the soma) to HFS (a, bottom panels). (b) In the simulation, clamping the extracellular potassium transient to experimental values slightly reduces the amplitude of GABA-mediated depolarization (middle). When effects of quinine on GABAA conductance (60% inhibition of GABAA) are included, the simulated voltage traces closely resembles the experimentally observed kinetics of hyperpolarization and diminished depolarization (b, right). The potassium transient is diminished, but not eliminated when GABAA is inhibited - also consistent with the experiment. Inset: magnification of magnitude and kinetics of the hyperpolarization with GABAA inhibition (black line) compared to control (black symbols). In the top panel, slower hyperpolarization occurs because of the decreased magnitude of current elicited by each GABA pulse. Note also the slower switch from hyperpolarization to depolarization in the presence of quinine in experiment (a, right) and simulation (bottom inset) (both marked with *). (B) Complete elimination of the extracellular potassium transient decreases GABAA-mediated depolarization (blue line) compared to control (black line). A similar decrease is observed when the potassium transient is unchanged, but the KCC2 transporter is insensitive to the potassium transient (red line). (C) An increase in extracellular volume of the dendritic compartments (22% of intracellular volume) (blue line) compared to control (15% of intracellular volume) (black line) has smaller effects on somatic membrane potential response in the model.