Structure of brain receptor involved in epilepsy and PMT identified

Washington, Mar 10 : Scientists at University of Cambridge in collaboration with colleagues at Aston University and the University of Alberta, have determined the structure of a receptor in the brain implicated in conditions such as epilepsy and pre-menstrual tension (PMT).

This receptor in the brain, called the GABA receptor, is also found to be highly sensitive to alcohol. GABAA receptors in the central nervous system play important roles in the body's response to gamma-aminobutyric acid (GABA), a chemical used by the brain to control certain functions.

The team researchers, led by Dr Mike Edwardson, has now understood how the receptors' sub-units are arranged, enabling the scientists to develop drugs to block or stimulate them, providing hope for sufferers of a range of conditions.

It's been shown that various types of GABAA receptor play a number of important roles in the body's control of behaviour and development.

But Cambridge scientists are the first to identify the structure of a type of GABAA receptor containing the so-called delta sub-unit. This receptor type is rarely found in the body but is believed to be strangely important in controlling our state of consciousness; it is highly sensitive to anaesthetics, and has been linked to epilepsy and pre-menstrual tension, and to the body's response to alcohol.

For the study, the researchers used an atomic force microscope for detecting the receptors. Later they applied tags to the receptors that bind to different sub-units. It is possible to identify these tags later with the microscope, which scans a probe over the surface of a sample.

After spotting the tags, it was possible for the team to identify where the various sub-units were located. This information may enable the researchers to build detailed models of the receptor which can be used to develop drugs to intervene in the signals that it receives.

"This type of GABA receptor plays a crucial role in the body's response to a range of stimuli. Scientists think that when there is a problem in the signalling, conditions such as epilepsy and PMT can occur. Now we have identified the detailed structure of the receptor we are in a better position to design drugs that bind to it, said Edwardson.

The research is published in the journal Molecular Pharmacology.

ANI