K. Liu Lin Thio, MD, PhD is a pediatric epileptologist who is interested in developing a research career in ion channel modulation because of its importance to understanding and treating neurological diseases such as epilepsy. He has extensive experience with cellular neurophysiology but would like to probe the molecular mechanisms underlying ion channel modulation. This requires that he learn the basic techniques of molecular biology, which is one of the goals of this proposal. Several neurological disorders including epilepsy may result, in part, from cortical inhibitory glycine receptor (GlyR) dysfunction. Thus, GlyR modulation is important to understanding and treating neurological disease. Although several modulators of GlyR have been identified, their mechanisms of action are unknown because quantitative pharmacological and electrophysiological studies have not been performed. This study proposes to test three hypotheses regarding the mechanism by which three known GlyR modulators act: 1) GlyR and gamma-aminobutyric acidA (GABAA) receptors interact through the cytoskeleton; 2) Sulfhydryl reducing agents inhibit GlyR by chelating extracellular zinc; 3) Potentiation and inhibition of GlyR currents by barbiturates occur at distinct sites. These hypotheses will be tested by studying the electrophysiological properties of native GlyR in cultured embryonic mouse hippocampal neurons and GlyR expressed at Xenopus oocytes and human embryonic kidney (HEK) 293 cells.
| Zhang, Hai Xia; Lyons-Warren, Ariel; Thio, Liu Lin (2009) The glycine transport inhibitor sarcosine is an inhibitory glycine receptor agonist. Neuropharmacology 57:551-5 |
| Zhang, Hai Xia; Thio, Liu Lin (2007) Zinc enhances the inhibitory effects of strychnine-sensitive glycine receptors in mouse hippocampal neurons. J Neurophysiol 98:3666-76 |
| Thio, L L; Zhang, H X (2006) Modulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine. Neuroscience 139:1315-27 |
| Karkar, Kameel M; Thio, Liu Lin; Yamada, Kelvin A (2004) Effects of seven clinically important antiepileptic drugs on inhibitory glycine receptor currents in hippocampal neurons. Epilepsy Res 58:27-35 |
| Thio, Liu Lin; Shanmugam, Ananth; Isenberg, Keith et al. (2003) Benzodiazepines block alpha2-containing inhibitory glycine receptors in embryonic mouse hippocampal neurons. J Neurophysiol 90:89-99 |
