1. Shisa7-Dependent Regulation of GABAA Receptor Single-Channel Gating Kinetics.
- Author
-
Castellano, David, Kunwei Wu, Keramidas, Angelo, and Wei Lu
- Subjects
- *
MEMBRANE proteins , *INFECTIOUS disease transmission - Abstract
GABAA receptors (GABAARs) mediate the majority of fast inhibitory transmission throughout the brain. Although it is widely known that pore-forming subunits critically determine receptor function, it is unclear whether their single-channel properties are modulated by GABAAR-associated transmembrane proteins. We previously identified Shisa7 as a GABAAR auxiliary subu-nit that modulates the trafficking, pharmacology, and deactivation properties of these receptors. However, whether Shisa7 also regulates GABAAR single-channel properties has yet to be determined. Here, we performed single-channel recordings of a2b3y2L GABAARs cotransfected with Shisa7 in HEK293T cells and found that while Shisa7 does not change channel slope conductance, it reduced the frequency of receptor openings. Importantly, Shisa7 modulates GABAAR gating by decreasing the duration and open probability within bursts. Through kinetic analysis of individual dwell time components, activation modeling, and macroscopic simulations, we demonstrate that Shisa7 accelerates GABAAR deactivation by governing the time spent between close and open states during gating. Together, our data provide a mechanistic basis for how Shisa7 controls GABAAR gating and reveal for the first time that GABAAR single-channel properties can be modulated by an auxiliary subu-nit. These findings shed light on processes that shape the temporal dynamics of GABAergic transmission. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF