Disulphide trapping of the GABA(A) receptor reveals the importance of the coupling interface in the action of benzodiazepines.

ABSTRACT:

Background and significance

Although the functional effects of benzodiazepines (BZDs) on GABA(A) receptors have been well characterized, the structural mechanism by which these modulators alter activation of the receptor by GABA is still undefined.

Experimental approach

We used disulphide trapping between engineered cysteines to probe BZD-induced conformational changes within the γ₂ subunit and at the α₁/γ₂ coupling interface (Loops 2, 7 and 9) of α₁β₂γ₂ GABA(A) receptors.

Key results

Crosslinking γ₂ Loop 9 to γ₂β-strand 9 (via γ₂ S195C/F203C and γ₂ S187C/L206C) significantly decreased maximum potentiation by flurazepam, suggesting that modulation of GABA-induced current (I(GABA)) by flurazepam involves movements of γ₂ Loop 9 relative to γ₂β-strand 9. In contrast, tet

SUBMITTER: Hanson SM 

PROVIDER: S-EPMC3041256 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature