Deciphering how general anesthetics work: the role of ion channels. Joel P. Goodman¹, Trevor Batty¹, Winnie Cheung¹, J. Ryan Jackson¹, Michael J. Murray², Gerald B. Call¹. 1) Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ; 2) Department of Anesthesiology, Mayo Clinic, Scottsdale, AZ.

   For more than 160 years, volatile anesthetics (VAs) have been used, yet the action of VAs upon the central nervous system is unknown. Recent evidence suggests that VA effects occur through multiple targets as opposed to a single common mechanism. Previous studies have indicated that ion channels may be VA targets. Our previous study was the first comprehensive analysis of ion channels in the response to isoflurane. We tested 359 ion channel genes within Drosophila melanogaster in an RNA interference (RNAi) screen to determine potential candidates for VA action. In the previous study, a small halothane screen was performed for data verification on a few ion channels; however, this revealed differences in their responses to the two VAs. As isoflurane and halothane have overall similar chemical structures, their responses were expected to be similar. This study explores the effects of halothane on ion channels and compares them with the isoflurane data. RNAi constructs were used for gene-specific silencing of ion channels throughout the genome. An inebriometer was used to quantitatively study the effects of halothane on the flies. The data were analyzed and compared with the isoflurane data. Of the 343 genes tested, 38.8% exhibited resistance which is very similar to the 39.7% resistant to isoflurane. Of all the genes that showed resistance to VAs, 69 were resistant to halothane only, 78 had resistance to isoflurane only, and 64 showed resistance to both VAs. In this shared resistance category, we found that 11 genes were either resistant or strongly resistant to both VAs. A more detailed analysis will be presented at the meeting. Analysis of the data revealed that there are significant differences between the actions of isoflurane and halothane on ion channels. These differences indicate that there are many potential pathways for VA action, even among those with similar chemical structures.