General anesthesia has been around for over 150 years, so I found it peculiar that we’ve only recently figured out its mechanism of action. Until recently the medical community understood the effectiveness of general anesthesia and how to manipulate it. We’ve understood that its solubility in lipids is correlated to its effectiveness. So, what changed?
June of last year, a paper was published to outline the mechanism of general anesthesia. The model organism used? Fruit flies. It turns out that the lipids in question are a subset of lipids in the plasma membrane that anesthesia activates, causing those lipids to excrete phospholipase D2 (PLD2). Phosphatidic acid and the disruption of lipid rafts in the membrane are contributors to the effects of anesthesia. The effects of both anesthetic and lipid disruption decreases both the concentration of a particular sphingomyelin (GM1) rafts and PLD2 localization to those said rafts. Anesthetic increases the regulation of phosphatidylinositol bisphosphate (PIP2). PIP2 pulls PLD2 out of the lipid rafts which disrupts GM1 localization. What causes the loss of consciousness is the potassium channel TREK1 being activated, which inhibits action potentials from being reached.
This discovery has shed light on how general anesthesia works and how our brain and consciousness are intertwined. This recent finding opens more doors for questions like how we fall asleep. Scientists are still out to understand why general anesthesia has evolved and the mechanism of action is for inhaled anesthesia.
https://www.medicalnewstoday.com/articles/scientists-unravel-the-mystery-of-anesthesia
Pavel, M. A., Petersen, E. N., Wang, H., Lerner, R. A., & Hansen, S. B. (2020). Studies on the mechanism of general anesthesia. Proceedings of the National Academy of Sciences, 117(24), 13757–13766. https://doi.org/10.1073/pnas.2004259117
Hello Diem,
ReplyDeleteI really enjoyed reading your post as one of my career interests is pediatric anesthesiology. I was honestly shocked to find out that the complete understanding of anesthesia was not determined until last year. This makes me wonder if the most recent publication of Standards of Monitoring by the Association of Anesthetists took these recent discoveries into consideration. Especially as a updated clause in these recommendations required that an age-adjusted MAC (minimum alveolar concentration) needs to monitored during use of inhaled anesthetic drugs. Especially since the PLD2 mentioned above is disrupted by TREK-1 activation from inhaled anesthetics. Another updated recommendation is that when inhaled anesthetic drugs are used that the attending anesthesiologist used ETAC (end-tidal anesthetic concentration) counts to determine the approximate concentration of anesthesia in patient's blood and brain to ensure that the lower and upper limits of concentration are not near. This ensures that while patient is under the influence of anesthesia the proper inhabitation of action potentials continues while other action potential such as in our heart do not become inhibited.
Klein, A. A., Meek, T., Allcock, E., Cook, T. M., Mincher, N., Morris, C., ... & Young, P. (2021). Recommendations for standards of monitoring during anaesthesia and recovery 2021: Guideline from the Association of Anaesthetists. Anaesthesia.