γ2L TM1 is critical for desensitization-deactivation coupling. A, Introducing γ2L subunit sequence of extracellular TM1 or the N terminus into the δ subunit increased fast desensitization (γ-δ M1e, δ(VYΔYF)). However, prolonged deactivation was only evident when both the N terminus and TM1 contained γ2L subunit sequence (γ-δ M1i). Note that receptors containing the δ(VYΔYF) subunit were divided into two groups: 13 of 21 that had fast desensitization, and eight that did not. The values for %τfast were calculated from the former group. The %τfast of all 21 patches was 21.8 ± 4.4%. Splice junctions of the chimeras are the same as the δ-γ M1e and M1i chimeras (Fig.4A). Horizontal calibration: 400 msec; vertical calibration: 53 pA for δ(VYΔYF), 11 pA for γ-δ M1e, and 17 pA for γ-δ M1i. B, Representative deactivation currents were normalized to the current amplitude at the offset of GABA application, and overlaid to illustrate the differences in rate. Wild-type δ and γ2L subunit-containing receptor currents were colored gray. Note that only receptors containing the γ-δ M1i chimera had both fast desensitization and prolonged deactivation resembling that of αβγ receptors. Scale bar, 100 msec.
