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In an earlier news article by xScience.info we reported on the results of two scientists of the Niels Bohr Institute, Copenhagen, Denmark . In a recent paper T. Heimburg and A. Jackson published a paper on the function of general anesthetics based on a thermodynamics approach. Their main message is basically that not proteins, but the physical behavior of the lipid membrane is the key factor in determining the action of anesthetics. In other views, however, the action of an anesthetic is rather based on an influence on specialized proteins, so called ion channels. In a recent study researchers focused on a direct influence on a potassium channel. Using chimeras of this protein they tried to identify the location to where an anesthetic binds. They claim that an important clue to how anesthetics work on the human body has been provided by the discovery of a molecular feature common to both the human brain and the great pond snail nervous system. These researchers hope that the discovery of what makes a particular protein in the brain sensitive to anesthetics could lead to the development of new anesthetics with fewer side effects. The study focuses on a particular protein found in neurons in the brain, known as a potassium channel, which is seen to stabilize and regulate the voltage across the membrane of the neuron. Communication between the millions of neurons in the brain which is the basis of human consciousness and perception, including perception of pain - involves neurons sending nerve impulses to other neurons. In order for this to happen, they claim that the stabilizing action of the potassium channel has to be overcome. Earlier studies on great pond snails by the same team identified that anesthetics seemed to selectively enhance the regulating action of the potassium channel, preventing the neuron from firing at all; meaning the neuron was effectively anesthetized. The researchers state that they have identified a specific amino acid in the potassium channel which, when mutated, blocks anesthetic activation. Lead author, Biophysics Professor Nick Franks from Imperial College London , explains how he sees that this will allow the importance of the potassium channel in anesthetic action to be established: “We've known for over 20 years now that these potassium channels in the human brain may be important anesthetic targets. However, until now, we've had no direct way to test this idea. Because a single mutation can block the effects of anesthetics on this potassium channel without affecting it in any other way, it could be introduced into mice to see if they also become insensitive to anesthetics. If they do, then this establishes the channel as a key target.” The group carried out their new study, published in the 20 July issue of the Journal of Biological Chemistry, by cloning the potassium channel from a great pond snail and then making a series of chimeric channels part snail and part human. The chimeras were used to try to identify the location of the precise amino acid to which the anesthetic binds on the potassium channel, giving the team a clearer picture than ever before of the precise mechanism by which anesthetics work. This kind of research, explains Professor Franks, is important because understanding exactly how anesthetics work may pave the way for the development of a new generation of anesthetics which solely affect specific anesthetic targets, which could potentially reduce the risks and side effects associated with current anesthetics. “At the moment, anesthetics have many unwanted side-effects on the human body such as nausea and effects on the heart. This is because our current drugs are relatively non-selective and bind to several different targets in the body. A better understanding of how anesthetics exert their desirable effects could lead to much more specific, targeted alternatives being developed, which could greatly reduce these problems”, he said. Contact: Danielle Reeves
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Imperial College London Source: EurekAlert! |
