JBC: Honey bee venom may help design new treatments to alleviate muscular dystrophy, depression and dementia

channelJuly 12, 2010 -- Researchers studying a toxin extracted from the venom of the honey bee are optimistic a recent discovery will aid in the design of new treatments for such conditions as muscular dystrophy, depression and dementia.

Apamin, a natural peptide toxin found in bee venom, is known for its ability to block a type of ion channel that enables a high-speed and selective flow of potassium ions out of nerves. The blocking of those channels in the brain causes nerves to become hyperexcitable, producing improved learning, which has implications for the treatment of dementia and depression. In addition, injection of apamin reduces symptoms in sufferers of myotonic muscular dystrophy (MD).

Until now, the exact mechanism by which apamin acts was poorly understood. In a study published in the Journal of Biological Chemistry, two teams from the University of Bristol and the University of Liege in Belgium describe the results of their joint work on the KCa2 potassium ion channels, also called SK channels.

Using computer models and a genetic approach, the researchers pinpointedy where apamin binds to block the channel. To block ion channels, most molecules act as a plug at their external mouth. Perhaps surprisingly, the researchers have discovered that apamin binds away from the channel pore and causes the shape of the channel to change through an "allosteric" mechanism, resulting in blockage.

This discovery could accelerate research into the design of new SK-channel blockers, which could imitate the action of apamin, to target SK channels in neural and muscular conditions, such as dementia, depression or MD.

Professor Neil Marrion of the University of Bristol's said, "Drug design depends on knowing the target. Our findings have provided a new approach to designing a therapeutic agent that could help with the treatment of a number of conditions."

"I am very enthusiastic about the results of our study, and I believe that, with the help of this piece of information, the targeting of these channels for the development of future drugs has been made easier," said professor Vincent Seutin of the University of Liège.

Citation

Allosteric block of KCa2 channels by apamin. Cedric Lamy, Samuel J. Goodchild, Kate L. Weatherall, David E. Jane,  Jean-Francois Liegeois, Vincent Seutin and Neil V. Marrion. First Published on June 18, 2010, doi: 10.1074/jbc.M110.110072

Neil Marrion at University of Bristol

Vincent Seutin at Université de Liège

Press release courtesy of Université de Liège