M2-M3 linker mutations αm, βm, or γm have subunit-specific effects on the intrinsic closed-open equilibrium and its modulation by DZ. Example currents from wild-type α1β2γ2 and gain-of-function α1(L9′T)β2γ2 receptors without and with M2-M3 linker mutations αm, βm, or γm. Currents are in response to 10 s pulses (black bars) of either 1 mM PTX, saturating 1–3 μM DZ (high affinity ECD site), or saturating GABA. Full concentration-response curves are shown in Figs. S1 and S2. Current block by the pore blocker PTX was used to assess the amount of spontaneous activity and to normalize DZ- and GABA-evoked responses from different oocytes. Currents are normalized from the zero-current baseline in PTX to the maximal GABA-evoked response.