Figure 6.

Mechanism of GABA_A receptor-mediated biphasic responses. A, Voltage-clamp recordings of the response of a neuron to different patterns of brief (20 ms) GABA applications The cell displayed a biphasic (outward/inward) response to GABA (left). Note that the second (middle) and third (right) application of GABA with 2 s intervals produce a monophasic inward current. Note also the small outward tail response after repetitive applications. B, Voltage-clamp recordings of the response of a neuron to pairs of brief (20 ms) muscimol applications (5, 10, 15, or 25 s interval; in the presence of CGP 54523). The second response was also monophasic when superimposed on the inward phase of the first response. Note that repetitive applications of muscimol do not induce the small outward tail. Inset, An enlargement on a faster timescale (same as in A). Traces are normalized to the amplitude of the first response to help comparisons. C, Voltage-clamp trace of a neuron responding to a train of focal electrical stimulations (short burst of 20 pulses, indicated by asterisks, at 25 ms intervals). Note the slowly developing inward phase and how individual synaptic currents have their polarity inverted (arrows) during this late inward phase. D, Effect of the replacement of the bicarbonate buffer by a HEPES buffer in the ACSF. Left, The inward phase of the biphasic responses observed near resting potential faded with time in HEPES. Right, At depolarized holding potentials (-39 mV), in which outward only responses were recorded, the decay phase of the responses was prolonged in HEPES. Traces are normalized to the amplitude of the first response to allow for comparison of the kinetics.