Fig. 6: Agonist-driven gating of the α1-GlyR’s pore does not require the capping of loop C. | Nature Communications

Fig. 6: Agonist-driven gating of the α1-GlyR’s pore does not require the capping of loop C.

From: Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation

Fig. 6: Agonist-driven gating of the α1-GlyR’s pore does not require the capping of loop C.

a, b Inward currents recorded from the indicated constructs in the whole-cell patch-clamp configuration in response to 20-ms (a) or 20-s (b) exposures to pH-4.5 extracellular solution. For the “wild-type” GLIC–α1-GlyR ECD–TMD chimera, responses are shown as the mean (black solid line) ± 1 SD (gray error bars) of normalized responses recorded from different whole-cell experiments. Averaged wild-type data in (a) correspond to a total of 77 responses recorded from 6 different cells, and those in (b) correspond to a total of 11 individual responses recorded from 11 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. In (a), the black dashed line denotes the current level at pH 7.4 at equilibrium, which (especially for the wild-type construct) was not zero. In (b), the black dashed line denotes the zero-current baseline. 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–α1-GlyR 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. This chimera’s deactivation kinetics are similar to those of the GLIC–β-GluCl construct (Fig. 5) and the adult-type muscle AChR. The pipette potential was –60 mV. The black dashed line denotes the zero-current baseline. Source data are provided as a Source Data file.

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