How Ion Channels Are Organized To Control Nerve Cell Communication

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How Ion Channels Are Organized To Control Nerve Cell Communication

http://www.medicalnewstoday.com/medicalnews.php?newsid=61572

The messages passed in a neuronal network can target something like

100 billion nerve cells in the brain alone. These, in turn

communicate with millions of other cells and organs in the body.

How, then, do whole cascades of events trigger responses that are

highly specific, quick and precisely timed? A team at the Weizmann

Institute of Science has now shed light on this mysterious

mechanism. Their discovery could have important implications for the

future development of drugs for epilepsy and other nervous system

diseases. These findings were recently published in the journal

Neuron.

The secret is in the control over electrical signals generated by

cells. These signals depend on ion channels - membrane proteins

found in excitable cells, such as nerve cells - that allow them to

generate electrical signals, depending on whether the channels are

opened or closed. Prof. Eitan Reuveny, together with Ph.D. students

Inbal Riven and Shachar Iwanir of the Weizmann Institute's

Biological Chemistry Department, studied channels that work on

potassium ions and are coupled to a protein called the G protein,

which when activated, causes the channel to open. Opening the

channel inhibits the conductance of electrical signals, a fact that

might be relevant, for example, in the control of seizures.

The G protein itself is activated by another protein, a receptor,

which gets its cue to carry out its task from chemical messengers

known as neurotransmitters. But neurotransmitters are general

messengers - they can inhibit as well as excite, and the receptors

can respond to either message. How, the scientists wanted to know,

is the G protein targeted so quickly and precisely to activate the

channel?

Reuveny and his team found that the receptor and G protein are

physically bound together in a complex, allowing the process to be

finely tuned. When the receptor receives a chemical message from the

neurotransmitter, it is already hooked up to the correct G protein.

After being activated by the receptor, the G protein changes shape,

opening the ion channel. The evidence for this complex structure

came from special technique called FRET (Fluorescence Resonance

Energy Transfer) that can measure the distance between two

molecules. The scientists observed that even without stimulation,

there is a lot of energy transfer between the G protein and the

potassium channel, suggesting that they are very close together.

Mutations in ion channels are likely to be involved in epilepsy,

chronic pain, neurodegenerative diseases and muscular diseases, and

ion channels are the target of many drugs. Understanding the basic

biological phenomena behind the way proteins organize themselves and

orchestrate biological processes may allow scientists to design

better or more efficient drugs.

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Prof. Eitan Reuveny's research is supported by the Y. Leon Benoziyo

Institute for Molecular Medicine; the Clore Center for Biological

Physics; and the Dr. f Cohn Minerva Center for Biomembrane

Research.