New research findings have positive implications for anti-smoking medication

If you have ever tried to give up smoking, suffered from a sleeping disorder or been struck down with a muscular disease, then new findings from a team of EU-funded researchers could be music to your ears. The findings, presented in the journal Public Library of Science (PLoS) Biology, show a number of new perspectives for the development of treatments for a variety of common conditions, in light of discoveries of the effects of the mysterious poison curare on the membrane proteins ion channels.

The research, which received funding from the NEUROCYPRES project under the 'Health' Thematic area of the Seventh Framework Programme (FP7), moves forward our knowledge of this poison which has long remained a mystery for scientists.

The human cell membrane - the wall of a living cell - is home to over 7,000 proteins, but so far researchers have only managed to identify the structure and function of 27 of these.

Ion channels are an important class of membrane proteins that are responsible for communication. Ion channels can be thought of as acting like switches, as they are shaped like microscopic pores that can open and close, and ions - charged particles - flow in or out of the cells through them. Poisons can disrupt this communication between cells in the body by blocking the ion channels.

Curare's paralysing effect on the structure of ion channels has been mapped out by the researchers through a series of three-dimensional (3D) images. Professor Ulens, one of the study's authors and Director of the Laboratory for Structural Neurobiology at Belgium's Katholieke Universiteit Leuven, explains the implications of the 3D images: "We are locksmiths who examine on an atomic scale how a key - the poison - fits the lock of a door - the ion channel - and how the key keeps the door locked. Some kinds of poison only fit one lock, but curare is a passkey that can close various ion channels."

Using 3D knowledge of the structure of this lock, the international team, from Belgium, Russia, the Netherlands and the United States now believe that passkey medications for a class of disorders can be developed; they also hope this to be the case for specific medication for one disorder, such as tobacco addiction for example, as nicotine affects one specific ion channel.

However, the mysterious nature of membrane proteins did pose some challenges for the researchers. X-ray crystallography, where crystals of proteins are grown in water and then X-rayed in order to expose and examine their structure, is the standard technique used to study proteins, yet growing crystals of fatty membrane proteins remains difficult due to the fatty nature of the cell membrane.

Professor Ulens describes how his team overcame this challenge: "For the past 10 years, researchers were forced to get in through the back door: a chemical copy of a section of ion channel. Chemically similar, but not porous. As a result, the formation of crystals was much easier. For the first time, our lab has applied the back entrance to the ion channel, which is sensitive to curare. We now have an image of how this class of ion channels recognises chemical substances."

Curare has such a paralysing effect that one of its components is actually used in lung surgery; it is also the poison that indigenous populations of the Amazon use while hunting by attaching the poison to their arrows in order to paralyse their prey.

All over the world, scientists have been trying hard to determine the 3D structure of membrane proteins as a key process for pharmacological research. The NEUROCYPRES project hopes to move forward this work and reveal the basic mechanisms of receptor functioning in order to open up new avenues of rational drug design.

Professor Ulens also hopes that his team's findings will move the development of medication in a new direction. He explains: "In the past, the pharmaceutical industry developed medications by releasing hundreds of thousands of substances into ion channels. If a certain substance caused a reaction, it would be tested on patients - a system of trial and error. Our research results in the more goal-oriented development of medications: by acquiring insight into the [3D] structure of an ion canal, specific medications that bind to the protein can be developed."

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