Dr. Harrison plans to develop his present studies on the cellular pharmacology of general anesthetic interactions with gamma-aminobutyric acid (GABA)-A receptors, and to pursue exciting new avenues utilizing single channel and molecular biological methods to uncover the basic mechanisms by which general anesthetics modulate GABA-A receptors. Specifically, the aims of the proposed research project will be to determine whether a range of general anesthetics interact with the GABA-A receptors of hippocampal neurons, and to investigate the pharmacological correlation between the ability of various agents to enhance the function of GABA and their ability to induce surgical anesthesia. The project will proceed to study the effects of the anesthetics on the kinetics of inhibitory synaptic currents mediated by GABA, and attempt to explain such effects by investigations at the level of single GABA-activated chloride channels in outside-out membrane patches. Finally, the project will utilize some of the recent advances in the molecular cloning of GABA-A receptors, by utilizing a transient expression system to study the pharmacology of GABA-A receptors of known subunit composition.
| Bloomenthal, A B; Goldwater, E; Pritchett, D B et al. (1994) Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+. Mol Pharmacol 46:1156-9 |
| Zimmerman, S A; Jones, M V; Harrison, N L (1994) Potentiation of gamma-aminobutyric acidA receptor Cl- current correlates with in vivo anesthetic potency. J Pharmacol Exp Ther 270:987-91 |
