MECHANISM OF ACTION OF VOLATILE ANESTHETICS

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The long term goal of this study is to understand the molecular basis of action of volatile anesthetics. Little is known about how volatile anesthetics produce reversible unconsciousness; this is true of our understanding at either the gross anatomical or subcellular/molecular level. This proposal uses a molecular genetic approach to try to understand the mechanism of action of volatile anesthetics in C. elegans. We have identified two uncoordinated mutants that differ greatly from the wild type worm in their sensitivity to the most potent volatile anesthetics. These mutant strains, unc-79 and unc-80, each behave normally in anesthetics when combined with other mutations, unc-1, unc-7, unc-9, or unc-24. Their behavior indicates changes at the sites of anesthetic action. We plan to use these mutations to understand the molecular nature of the site of anesthetic action. The specific aims of this proposal are: 1. To characterize the genetic control of anesthetic response in C. elegans by isolating additional mutations which alter the site of action of volatile anesthetics. 2. To further characterize the mutations we have recently identified as altering the anesthetic site of action. This will entail mapping these genes and determining their interaction with the other involved genes. Ultimately we wish to determine a functional pathway which controls response to these agents. 3. To clone unc-1 using the transposon tagging technique. We plan to analyze the primary structure of the corresponding protein products, and search for homologous protein products in more complex organisms. This information will be combined with the data being accumulated by others studying unc-79 and unc-80 in our laboratory.