Scientists A Step Closer To Understanding How Anesthetics Work In The Brain

Thursday, July 19, 2007

New study using human-snail chimeras shows how anesthetics target one specific protein in the brain

The study focuses on a particular protein found in neurons in the brain, known as a potassium channel, which stabilities and regulates 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, 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 new research has 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 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 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.

Source: Imperial College London