Experiments in one of the oldest forms of life on Earth are helping to answer basic questions about how general anesthesia works, according to a study in the January issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).
"Although the anesthetizing properties of ether have been known for over 150 years, scientists still do not know how ether and the other inhaled anesthetics act," comments Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia & Analgesia. "One challenge has been the diverse nature of substances that produce anesthetic effects, ranging from an atom (xenon), to a simple molecule (nitrous oxide), to a variety of organic solvents. How could such a diverse set of molecules cause a specific behavior: reversible loss of consciousness? The search has been complicated by our inability to find a suitably simple system in which to study the action of inhaled anesthetics."
Simplest Life Form Provides Clues to Anesthetic Actions
It is hard to envision a simpler creature than Gloeobacter violaceus, a dark purple cyanobacterium. Cyanobacteria are primitive algae, dating back more than 3 billion years. They have been well studied, and their DNA has been completely sequenced.
"Like all cellular life, these one-celled organisms must control the movement of ions and water in and out of the cell," explains Dr. Shafer. "They do this using proteins in the cell membrane that are similar to those found in all plants and animals."
Scientists from the University of California at San Francisco (UCSF) and the prestigious Pasteur Institute, Paris, have teamed up to study the effects of anesthetics on the primitive proteins controlling ion and water flow in and out of the cell. As reported in the new study, they discovered that proteins in the cell membranes of G. violaceus are very sensitive to commonly used anesthetics: both inhaled anesthetics, like desflurane, halothane, isoflurane, sevoflurane, and xenon; and intravenous anesthetics, like propofol and etomidate.
Dr. James M. Sonner, leader of the UCSF team, comments, "These findings support the conjecture that the capacity to respond to inhaled anesthetics arose in organisms lacking nervous systems." In an accompanying editorial, Carl Lynch at the University of Virginia notes that studies of these very simple organisms "will begin to answer how our structurally simple [anesthetic] agents produce their panoply of actions."
Having demonstrated sensitivity to anesthetics, the scientific team is now trying to understand exactly how anesthetics work in these one-celled creatures. "That knowledge may answer one of the oldest questions in pharmacology: what is the exact mechanism by which consciousness is temporarily suspended by the action of anesthetic drugs?" adds Dr. Shafer. "In the process, the researchers may also learn why one-celled organisms that date back billions of years and do not have nervous systems respond to inhaled and intravenous anesthetics—even though these drugs do not exist in nature."
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