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• W4212825001 abstract "Abstract GABA A receptors (GABA A Rs) 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 GABA A R-associated transmembrane proteins. We previously identified Shisa7 as a GABA A R auxiliary subunit that modulates the trafficking, pharmacology, and kinetic properties of these receptors. In particular, Shisa7 accelerates receptor deactivation; however, the underlying mechanisms by which Shisa7 controls GABA A R kinetics have yet to be determined. Here we have performed single-channel recordings and find that while Shisa7 does not change channel slope conductance, it reduces the frequency of openings. Importantly, Shisa7 modulates GABA A R gating by decreasing the duration and open probability (P o ) within bursts. Kinetic analysis of dwell times, activation modeling, and macroscopic simulations indicate that Shisa7 accelerates GABA A R deactivation by governing the time spent between close and open states during gating. Together, our data provide a mechanistic basis for how Shisa7 controls GABA A R gating kinetics and reveal for the first time that GABA A R single-channel properties can be modulated by an auxiliary subunit. These findings shed light on processes that shape the temporal dynamics of GABAergic transmission." @default.
• W4212825001 created "2022-02-24" @default.
• W4212825001 creator A5035939534 @default.
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• W4212825001 date "2022-02-13" @default.
• W4212825001 modified "2023-09-28" @default.
• W4212825001 title "Shisa7-dependent regulation of GABAA receptor single-channel gating kinetics" @default.
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• W4212825001 doi "https://doi.org/10.1101/2022.02.11.480135" @default.
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