Understanding the mechanisms of GABA type-A receptor activation and drug modulation (2012–2014)
The GABA-A inhibitory synaptic receptor is the target for anaesthetics and therapeutic drugs used to treat conditions such as anxiety and epilepsy. We currently have no quantitative mechanism for understanding how GABA-A receptors are activated or how therapeutic drugs modulate their activity. We propose to develop such a mechanism based on the analysis of GABA-A receptor single channel kinetics. This model will accurately predict how synaptically-localised receptors of defined subunit composition will respond to agonists and therapeutic drugs. This information will allow us to design new drugs that modulate GABA-A receptors in therapeutically useful ways and to select the most appropriate treatments for pathologies involving this receptor.