Phyisicans have used general anesthetics in one form or another for over a century. Yet, in many cases, the specific mechanisms at the molecular level of how anesthetics function are poorly understood. For many researchers conducting basic science in anesthesiology, expanding our knowledge of the processes through which general anesthetics function is a an important goal: not only to answer scientific questions, but also to provide data that can allow anesthesiologists to utilize anesthetics more effectively. Illuminating these questions is one of the goals of the researchers in the Labortatory of Hugh C. Hemmings Jr., MD, PhD, at Weill Cornell Anesthesiology.
Karl Herold, MD, PhD, of the Hemmings Lab, was first author of a recent article in the Journal of General Physiology that uncovered heretofroe unknown information about the molecular process behind the functioning of commonly-used general anesthetics such as isoflurane. Dr. Herold, Dr. Hemmings, and their team - including Dr. Olaf Andersen of the Department of Physiology and Biophysics - sought to test which of the two hypothesized mechanisms for the functioning of general anesthesia is most responsible. General anesthetics function at the cellular level by changing the ways in which nerve cells (neurons) chemically and electrically interact with each other - the process of synaptic transmission. Anesthetics inhibit some normal synaptic transmissions, while facilitating others. The question of how this process unfolds below the cellular level - at the molecular level - is the question the Hemmings Lab team sought to answer. Do anesthetics act on the neurons' cell membrane (the lipid bilayer) or do they act by affecting the electrical transmission within the membrane's protein cells?
Dr. Herold's article reveals that the evidence supports the second hypothesis. After examining the effects of isoflurane and several flourobenzene anesthetics on neuronal cells, the Hemmings Lab found that the cell membrane proteins responsible for electrical transmission, the sodium channels, were the main areas inhibited by clinical-level doses of general anesthetics. The neurons' cell membrane itself was only affected by extremely high levels of anesthetic that would never be used in patients. The hope is that these findings can be used by anesthesiologists to develop more effective anesthetics and also decrease potential side effects.
Links
- Weill Cornell Medical College Press Release
- Article at Journal of General Physiology
- Hemmings Lab website