The desensitization pathway of GABA_A receptors, one subunit at a time.

ABSTRACT: GABA_A receptors mediate most inhibitory synaptic transmission in the brain of vertebrates. Following GABA binding and fast activation, these receptors undergo a slower desensitization, the conformational pathway of which remains largely elusive. To explore the mechanism of desensitization, we used concatemeric α1β2γ2 GABA_A receptors to selectively introduce gain-of-desensitization mutations one subunit at a time. A library of twenty-six mutant combinations was generated and their bi-exponential macroscopic desensitization rates measured. Introducing mutations at the different subunits shows a strongly asymmetric pattern with a key contribution of the γ2 subunit, and combining mutations results in marked synergistic effects indicating a non-concerted mechanism. Kinetic

SUBMITTER: Gielen M 

PROVIDER: S-EPMC7585415 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature