Benzodiazepine (BZ) modulation of GABAAR surface levels and synaptic inhibition.
BZ are effective and fast acting therapeutic agents used to treat insomnia, anxiety and epilepsy. However problems with BZ tolerance, dependence and withdrawal limit their clinical use and have associated problems. The GABAAR BZ binding site is formed at the interface between α1, α2, α3, or α5 subunits in combination with a γ subunit and potentiates the response elicited by GABA. To understand the development of BZ tolerance and overcome the molecular challenges of GABAAR complexity, we are utilizing novel and sensitive optical methods to study the cell surface dynamics and trafficking of GABAAR subtypes. Incorporation of an N-terminal pH-sensitive GFP reporter in GABAAR subunits allows the specific visualization of surface receptor subtypes in living neurons, as shown in the movie below.
BZ are effective and fast acting therapeutic agents used to treat insomnia, anxiety and epilepsy. However problems with BZ tolerance, dependence and withdrawal limit their clinical use and have associated problems. The GABAAR BZ binding site is formed at the interface between α1, α2, α3, or α5 subunits in combination with a γ subunit and potentiates the response elicited by GABA. To understand the development of BZ tolerance and overcome the molecular challenges of GABAAR complexity, we are utilizing novel and sensitive optical methods to study the cell surface dynamics and trafficking of GABAAR subtypes. Incorporation of an N-terminal pH-sensitive GFP reporter in GABAAR subunits allows the specific visualization of surface receptor subtypes in living neurons, as shown in the movie below.
