摘要：

Introduction: Volatile anesthetics (VAs) have been used for more than 160 years, yet their mechanism of action on the central nervous system is unknown.Recent evidence suggests that VA effects occur through multiple targets as opposed to a single common mechanism and that the action of VAs on specific ion channels produces general anesthesia. Hypothesis: Because isoflurane and halothane have similar chemical structures with relatively similar pharmacodynamic effects in most animal models, these VAs act through the same ion channels. Methods: We crossed Drosophila melanogaster stocks that possessed a transgenic construct that induces suppression of specific ion channel gene of interest via RNA interference (RNAi) with a stock that causes the expression of this transgenic RNAi construct specifically in the nervous system.Previously, we tested 359 individual ion channel genes within Drosophila melanogaster in an RNAi screen to determine potential can - didates for VA action with isoflurane.Using a previously validated airtight inebriometer and protocol, we placed a minimum of 100 flies into a column of the inebriometer to expose the flies with the suppressed ion channel to 1% isoflu - rane at a flow of 0.5 L/min.We determined the flies' resistance or sensitivity by evaluating their response to the VA in comparison to the 95% pre - diction intervals calculated from the results from separate control fly crosses.For this study, the screen was performed a second time using 340 of the original 359 RNAi stocks with 2% halothane as the VA. Results: Of the 340 genes tested, almost 39% produced resistance in the flies, which is very similar to the 40% resistant observed with iso - flurane.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 resis - tant or strongly resistant to both VAs. Conclusion: The expression of many specific ion channel genes being reduced produced resistance to the effects of both VAs.Many of these genes produced resistance in flies to both VAs.How - ever, we rejected the null hypothesis because ion channels that, when silenced, conferred resistance to anesthesia depended on whether the fly was exposed to isoflurane or halothane.Therefore, it appears that similar anesthetics work through both shared and distinct mechanisms.

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