Fig. 5: Agonist-driven gating of β-GluCl’s pore does not require the capping of loop C.
From: Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation

a, b Inward currents recorded from the indicated constructs in the whole-cell patch-clamp configuration in response to 20-ms (a) or 1-min (b) exposures to pH-4.5 extracellular solution. For the “wild-type” GLIC–β-GluCl ECD–TMD chimera, responses are shown as the mean (black solid line) ± one standard deviation (SD; gray error bars) of normalized responses recorded from different whole-cell experiments. Averaged wild-type data in (a) correspond to a total of 98 responses recorded from 9 different cells, and those in (b) correspond to a total of 9 responses recorded from 9 different cells. Each individual normalized response shown for the loop-C-deleted mutant was recorded from a different cell. The pipette potential was –60 mV. c Inward currents recorded from the indicated constructs in the whole-cell patch-clamp configuration in response to 20-ms pulses of agonist. The latter was pH 4.5 for the GLIC–β-GluCl chimera; 100-μM ACh for both the α7 AChR and the α1β1δε AChR; 200-μM ACh for the α3β4 AChR; and 1-mM GABA for both heteromeric GABAARs. Each displayed trace is the average of several normalized responses recorded from different cells; for the sake of clarity, only the mean of each distribution is shown. The traces were horizontally aligned at their half-activation times. The chimera’s currents decay (deactivate) more slowly than those of the α7 AChR, faster than those of the ganglionic (α3β4) AChR and heteromeric GABAARs, and at nearly the same rate as those of the adult-type muscle (α1β1δε) AChR. The pipette potential was –60 mV. d Whole-cell currents recorded under KCl-dilution conditions (high KCl concentration in the pipette solution; low, in the extracellular solution); the pipette potentials indicated next to each trace were corrected for the liquid-junction potential that arises between these two solutions. The indicated equilibrium potentials (ECl– and EK+) were calculated at 22 °C using ion concentrations. The reversal potential of the chimera was very close to the equilibrium potential for Cl– (ECl–). For all panels, black dashed lines denote the zero-current baseline. Source data are provided as a Source Data file.