Figure 1.

Dose-dependent effect of THDOC on GABA-mediated currents in α5β3γ2L GABA_A receptors. THDOC increased the amplitude and prolonged the decay of the responses to 0.3 µM GABA (relative to the first peak without THDOC application). Note the outward shift in baseline holding current when THDOC (30–300 nM) is applied (see arrows pointing to the shift). α5β3γ2L-expressing HEK-293 cells were exposed to a series of prolonged applications of low-concentration GABA (6 s, 0.3 µM GABA) to mimic the tonic activation of extra-synaptic GABA_A receptors. Except for the first application, all GABA applications in each series were performed in combination with THDOC, delivered in incremental concentrations ranging from 30 to 300 nM. Each application of GABA and THDOC in combination was preceded by a 20 s exposure to THDOC only. The current responses were continuously recorded with the holding membrane potential −17 mV (corrected for the liquid junction potential).