Fellow

Trevor Smart is Schild Professor of Pharmacology, University College London He is internationally-recognised for his contributions to our understanding of the GABAA receptor, the most important inhibitory neurotransmitter receptor in the mammalian brain. His early studies resulted in the first description of an all-encompassing kinetic model for drug-receptor antagonism enabling one of the first demonstrations of antagonists affecting ion channel gating. Key for many future molecular studies of GABAA receptors was his breakthrough description of the functional expression of GABA and glutamate receptors in vitro, using the Xenopus oocyte system. So successful was this approach that the preparation became an essential laboratory tool worldwide. Trevor Smart is probably best known for his seminal correlative electrophysiological/molecular studies. He discovered that brain GABAA receptors can be regulated by endogenous molecules and ions, and showed that physiological levels of zinc affect GABA release. He subsequently proved that zinc interacts directly with the receptor, depending on its subunit composition, thereby providing functional evidence of GABAA receptor heterogeneity. By developing structural homology modelling of GABAA receptors, he deduced the locations of several zinc binding sites. He also established how protons affect GABAA receptors; discovered the proton site in the ion channel, and described its dependence on subunit composition and importance for ischaemia. Trevor Smart also reported the first molecular mechanisms for regulating GABAA receptors by phosphorylation. The interactions of protein-partners with GABAA receptors have yielded new insight into how these receptors are dynamically-regulated on the cell membrane and these studies have helped identify a new form of inhibitory synaptic plasticity as well as leading to the development of a new method for monitoring the trafficking of functional GABAA receptors in real-time on surface membranes of live neurones. In addition to his outstanding research record he is a strong advocate for the discipline of Pharmacology.