Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers 'see' structure of open nicotinic acetylcholine ion channels

08.04.2008
The neurotransmitter acetylcholine is an essential chemical communicator, carrying impulses from neurons to skeletal muscle cells and many parts of the nervous system.

Now researchers at the University of Illinois have painstakingly mapped the interior of a key component of the relay system that allows acetylcholine to get its message across. Their findings, which appear in the current issue of Nature Structure & Molecular Biology, reveal how the muscle nicotinic acetylcholine receptor responds to a burst of acetylcholine on the surface of a cell.

The muscle nicotinic receptor is a neurotransmitter-gated ion channel. This “gate” regulates the flow of information, in the form of charged particles, or ions, across the cell membrane. Although normally closed, when the ion channel encounters acetylcholine – or nicotine – on the surface of the cell the interaction causes the gate to open, allowing positively charged ions (called cations) to flow into the cell.

Scientists have tried for decades to understand the mechanism that allows these channels to open. Using cryo-electron microscopy, in which samples frozen at extremely low temperatures are examined under an electron microscope, some researchers obtained images of the closed ion channel. More recently, others used X-ray crystallography to image the closed-channel conformation. This technique involves crystallizing the protein, creating a lattice that reveals many details of its three-dimensional structure.

... more about:
»Grosman »Ion »Living »acetylcholine »amino »nicotinic »structure

But until the Illinois team developed a new method for probing the interior of the open channel, no studies had been able to infer the structure of the open channel conformation in a living cell. The Illinois team was able to do this by exploiting electrical properties of these membrane proteins.

Much like the flow of electrons through an electrical wire, the flow of ions through a cell membrane is a current. In the 1970s, two German researchers developed a technique for measuring the current through a single ion channel, an innovation (known as the patch-clamp technique) that won them a Nobel Prize in 1991. Claudio Grosman, a professor of molecular and integrative physiology at Illinois, and Gisela D. Cymes, a postdoctoral associate in his lab, adopted this technique, and predicted that they could use it as a tool for what they call “in vivo, time-resolved structural biology.”

In a study published in 2005, the Grosman lab showed that ionizable amino acids (that is, those that may alternately be charged or neutral) can be engineered into the inner lining of the channel pore. These changes to the amino acid sequence alter the current, revealing the structure of the open-channel conformation in unprecedented detail.

“As the ionizable amino acids bind and release protons from the watery environment, the pore gains or loses a positive charge that interferes with the normal flow of cations through the channel,” Grosman said.

After analyzing the data, Grosman’s team demonstrated that the discrete changes in current reflect the position of each mutated amino acid in the channel and the extent to which water molecules penetrate the membrane protein.

This approach allowed Grosman’s team to map the relative position of every amino acid that formed the ion channel.

The new study extends this work to more distant portions of the protein.

After comparing these findings to direct studies of the structure of the closed channel, Grosman concluded that the conformational changes that allow the channel to open are quite subtle. The five subunits that make up the protein channel do not rotate or pivot dramatically when opening the gate.

“There are many good reasons why I think a subtle conformational change is advantageous from an evolutionary point of view,” Grosman said.

Muscle nicotinic receptors must respond to acetylcholine with staggering speed, opening within microseconds of their exposure to the neurotransmitter.

“These ion channels are meant to be quick,” he said. “If they are too slow, we have disease.”

Grosman said that the approach developed in his lab is the first to allow scientists to infer the structure of an ion channel in its open conformation as it functions in a living cell.

“I know when the protein is open, because in single-molecule experiments the distinction between open and closed conformations is simple; the channel either passes a current or not,” he said.

In a living cell the protein responds, in measurable ways, to changes in its structure and environment, he said. “It’s not frozen at super low temperatures. It’s not in a crystalline lattice. The cells are alive at the beginning of the experiment and when we finish the experiment, the cells keep living."

Diana Yates | University of Illinois
Further information:
http://www.uiuc.edu

Further reports about: Grosman Ion Living acetylcholine amino nicotinic structure

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>