Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson scientists uncover new clues to how crucial molecular gatekeepers work

12.10.2005


Understanding how voltage-gated ion channels operate is requisite for improving disease treatment



One of the biggest mysteries in molecular biology is exactly how ion channels – tiny protein pores through which molecules such as calcium and potassium flow in and out of cells – operate. Such channels can be extremely important; members of the voltage-gated ion channel family are crucial to generating electrical pulses in the brain and heart, carrying signals in nerves and muscles. When channel function goes awry, the resulting diseases – known as channelopathies, including epilepsy, a number of cardiomyopathies and cystic fibrosis – can be devastating.

Ion channels are also controversial, with two competing theories of how they open and close. Now, scientists at Jefferson Medical College, reporting October 6, 2005 in the journal Neuron, have detailed a part of this intricate process, providing evidence to support one of the theories. A better understanding of how these channels work is key to developing new drugs to treat ion channel-based disorders.


According to Richard Horn, Ph.D., professor of physiology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, voltage-gated ion channels are large proteins with a pore that pierces the cell membrane. They open and close in response to voltage changes across the cell membrane, and the channels determine when and which ions are permitted to cross a cell membrane.

In the conventional theory, when an electrical impulse called an action potential travels along a nerve, the cell membrane charge changes. The inside of the cell (normally electrically negative), becomes more positive. In turn, the voltage sensor, a positively charged transmembrane segment called S4, moves towards the outside of the cell through a small molecular gasket called a gating pore. This movement somehow causes the ion channel to open, releasing positively charged ions to flow across the cell membrane. After the action potential is over, the cell’s inside becomes negative again, and the membrane returns to its normal resting state.

The more recent and controversial theory proposed by Nobel laureate Roderick MacKinnon of Rockefeller University holds that a kind of molecular paddle comprised of the S4 segment and part of the S3 segment moves through the cell membrane, carrying S4’s positive charges with it across the lipid. As in the conventional theory, the S4 movement controls the channel’s opening and closing. The two theories differ in part because the paddle must move its positive charges all the way across the cell membrane. The conventional theory says that charges move a short distance through the gating pore.

In the current work, Dr. Horn and colleague Christopher Ahern, Ph.D., a research assistant in the Department of Physiology at Jefferson Medical College, showed that the field through which the voltage sensor’s charges moved is very short, lending support to the conventional model.

"Using a molecular tape measure with a very fine resolution – 1.24 Angstroms – we tethered charges to the voltage sensor," Dr. Horn explains. "When the tether is too long, the voltage sensor can’t pull it through the electric field," meaning the electric field is highly focused.

"This is another nail in the coffin of the paddle model," he says, "because the thickness of the electric field is much smaller than predicted by that model. The measurement is unambiguous in terms of the relationship between length of the tether and how much charge gets pulled through the electric field.

Next, the researchers are tackling the relationship between S4’s movement and the gates that open and close the channels.

Steve Benowitz | EurekAlert!
Further information:
http://www.jefferson.edu

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>