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My research is focused on understanding the molecular mechanisms of anesthetic action on ligand-gated ion channels. General anesthetics are administered to more than 25 million patients in the U.S each year, but the underlying molecular mechanisms are not understood. Cys-loop ligand-gated ion channels such as the GABAA, 5-HT3, glycine, and nicotinic acetylcholine receptors form a superfamily of anesthetic-sensitive receptors that are thought to play important roles in mediating the desirable clinical actions and undesirable side-effects of general anesthetics. NMDA receptors are glutamatergic ligand-gated ion channels that are also important targets of general anestheticsMy laboratory uses electrophysiological techniques to define the actions of general anesthetics on ligand-gated ion channels. Our recent focus has been on 5-HT3 and NMDA receptors. By applying electrophysiological techniques with very rapid solution exchange, we are measuring 5-HT3 receptor activation, deactivation, and desensitization rates and then using computer kinetic modeling to understand how these receptors work and what anesthetics do.
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