Scientists close in on anaesthetic action

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.

The first operation under anesthesia (ether) in 1846. It is only now that the action of anaesthetics is being fully understood

Researchers hope that the discovery of what makes a particular protein in the brain sensitive to anaesthetics, could lead to the development of a new form with fewer side effects.

The study focuses on a particular protein found in neurons, known as potassium channels, which stabilise and regulate the voltage across the membrane of the cell. 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.

Biophysics Professor, Nick Franks from Imperial College London said: “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.”

The new research has identified a specific amino acid in the potassium channel which, when mutated, blocks anaesthetic activation which will allow the importance of the potassium channel in anaesthetic action to be established.

“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,” said Professor Franks.

The finding is important because understanding exactly how anaesthetics work may pave the way for the development of a new generation of anaesthetics which solely affect specific anaesthetic targets, potentially reducing the risks and side effects associated with current anaesthetics.

“At the moment, anaesthetics 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 anaesthetics exert their desirable effects could lead to much more specific, targeted alternatives being developed, which could greatly reduce these problems,” said Professor Franks.

The group published their study in the Journal of Biological Chemistry.