Microbiology/Genetics

Mystery Solved: How Anesthetics Work

They block the calcium ion channel TRPC5

By Stefan Anitei, Science Editor

2nd of April 2008, 06:41 GMT

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This is a great mystery that has been finally solved: how do most anesthetics work. And it started with almost the only anesthetic our grandparents could name, the chloroform, which has been used for over 150 years. The discovery was made by accident by Leeds University Dr. Yahya Bahnasi.

"We take general anesthesia for granted nowadays, but it's still true

to say that we don't know exactly how it works on a molecular level. However, I was examining the relationship between lipids and atherosclerosis and it just so happened that the lipids I was using were supplied already dissolved in chloroform. I noticed that the chloroform inhibited, or blocked, the calcium ion channel TRPC5 - it was quite a striking effect," said Bahnasi, a qualified medical doctor on an Egyptian Ministry of Higher Education Scholarship at the University's Faculty of Biological Sciences.

Ion channels are tube proteins embedded in the cell membranes that permit electrically charged atoms to cross cell membranes accomplishing various functions, from pain transmission to the neuronal transmission, timing of the heart beat and muscle contraction. TRPC5 calcium ion channels are encountered in many tissues, but their maximum density is found on the brain cells.

"We know that this ion channel plays a signaling role in the central nervous system, which regulates the conscious and unconscious states, so I was left wondering whether inhibiting this calcium ion channel was one mechanism by which anesthesia works," said Bahnasi.

Several other anesthetic chemicals, delivered both intravenously and inhaled, were proved to act in the same way: by blocking the TRPC5 ion channels.
"The discovery opens up the opportunity to design and develop new generations of anesthetics which directly target TRPC5, but with minimized side effects. Of course there are multi-molecular events that work together in anesthesia, and inhibiting the TRPC5 ion channel may just be one of them. But it's a great start in piecing together the underlying mechanisms and providing a novel molecular target for new drug design," said Bahnasi.

TAGS:

anesthetics | brain | ion | calcium | channel

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