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

An important clue to how anaesthetics 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, scientists now report. Researchers hope that the discovery of what makes a particular protein in the brain sensitive to anaesthetics could lead to the development of new anaesthetics with fewer side effects.

The study focuses on a particular protein found in neurons in the brain, known as a potassium channel, which stabilises 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 stabilising action of the potassium channel has to be overcome. Earlier studies on great pond snails by the same team identified that anaesthetics seemed to selectively enhance the regulating action of the potassium channel, preventing the neuron from firing at all -- meaning the neuron was effectively anaesthetised.

The new research has identified a specific amino acid in the potassium channel which, when mutated, blocks anaesthetic activation. Lead author, Biophysics Professor Nick Franks from Imperial College London, explains how this will allow the importance of the potassium channel in anaesthetic action to be established:

"We've known for over 20 years now that these potassium channels in the human brain may be important anaesthetic targets. However, until now, we've had no direct way to test this idea. Because a single mutation can block the effects of anaesthetics 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 anaesthetics. 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 anaesthetic binds on

Refs
HOME
Resources
Snapshots
Anaesthesia
Anaesthesia (pdf)