Faculty Profile

David S. Weiss, Ph.D.

Research Interests

y-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. Dysfunctions of GABA-mediated inhibition have been implicated in the etiology of a variety of brain disorders such as epilepsy. Furthermore, GABA receptors are a target for a variety of therapeutic, neuroactive compounds such as benzodiazepines and barbiturates.

GABA, released at presynaptic terminals, diffuses across the synaptic cleft and binds to the pentameric GABA receptors on the postsynaptic membrane. We address a variety of questions directed at understanding how GABA receptors work. First and foremost, what is the mechanism by which the binding of agonist (GABA) leads to the opening of the chloride-selective pore? Also, once open, how does the pore allow 106 chloride ions per second to flow across the membrane, but essentially no cations? A third question addresses the mechanism by which allosteric compounds such as benzodiazepines (diazepam) and barbiturates (pentobarbital) alter channel function. Finally, how does the GABAergic neuron regulate the number of postsynaptic GABA receptors on the cell surface. To address these questions we use a variety of molecular biological, biochemical, pharmacological, electrophysiological, and biophysical techniques to gain insight into the structure and function of GABA receptor activation, permeation, modulation, and regulation.

Education B.A., University of North Carolina at Chapel Hill, 1980 Ph.D., Baylor College of Medicine, 1987
Selected Publications

Khatri A, Weiss DSThe role of Loop F in the activation of the GABA receptor. J Physiol. 2010 Jan 1;588(Pt 1):59-66.

Li P, Khatri A, Bracamontes J, Weiss DS, Steinbach JH, Akk G. Site-specific fluorescence reveals distinct structural changes induced in the human rho 1 GABA receptor by inhibitory neurosteroids. Mol Pharmacol. 2010 Apr;77(4):539-46.

Khatri A, Sedelnikova A, Weiss DS.  Sructural Rearrangements in Loop F of the GABA Receptor Signal LIgand Binding, Not Channel Activation.  Biophys J. 2009 Jan:96(1):45-55.