Modes and models of GABAAreceptor gating

摘要: Upon activation by agonist, the type A γ-aminobutyric acid receptor (GABAR) ‘gates’, allowing chloride ions to permeate membranes and produce fast inhibition of neurons. There is no consensus kinetic model for GABAR gating mechanism. We expressed human α1β1γ2S GABARs in HEK 293 cells recorded single channel currents cell-attached configuration using various GABA concentrations (50–5000 μm). Closed open events occurred individually clusters that had at least three different modes were distinguishable probability (PO): High (PO= 0.73), Mid 0.50), Low 0.21). used a critical time isolate shorter bursts openings thus eliminate long-lived, desensitized events. Bursts from all contained closed components. employed maximum likelihood fitting, autocorrelation analysis macroscopic current simulation distinguish schemes. The ‘core’ scheme most models two states preceded an state (C1⇌ C2⇌ O1). best-fitting third connected C1 second (O2) C2. state, whose occupancy varied greatly between modes, could be either O2 or estimated rate constants identical, independent binding steps globally fitting data across ranging 50 1000 μm. For highly ranked were: k+= 3 μm−1 s−1 k–= 272 (KD= 91