Structural Determinants of Fast Desensitization and Desensitization–Deactivation Coupling in GABAAReceptors

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Fig. 1.
Fig. 1.

Macroscopic kinetics of αβδ and αβγ GABAAR isoforms. A, Rapid biphasic desensitization and prolonged deactivation were typical for αβγ receptors in response to a 400 msec pulse of 1 mm GABA. In this and all subsequent figures, outside-out patches excised from acutely transfected fibroblasts (mouse L929 and HEK293T) were exposed to GABA using the concentration-jump technique (see Materials and Methods). Patches were generally clamped at −50 to −75 mV. The traces shown are the average of multiple GABA-evoked currents from a single patch. Desensitization was described by the sum of fast (τfast) and slow (τslow) exponential functions. Deactivation was fit with one or two exponential functions, and the weighted deactivation τdeact is shown.B, Representative patch containing αβδ receptors showed minimal desensitization during a 400 msec pulse of GABA. This current was described by a single exponential decay function, τ = 34 msec. Deactivation of this isoform (τdeact = 54.7 ± 4.8 msec) was rapid compared with the α1β3γ2L isoform (τdeact = 171.8 ± 20.4 msec).C, Overlay of rescaled traces from A andB to emphasize the differences in fast desensitization (p < 0.0001) and deactivation (p < 0.0001) between these isoforms. The αβδ current was colored gray for clarity. Thecurved lines in each trace are the fitted exponential functions describing the desensitization time course.

  1. The Journal of Neuroscience vol. 21 no. 4 1127-1136
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