Featured Research

from universities, journals, and other organizations

Structure of sodium channels different than previously believed

Date:
April 17, 2014
Source:
University of Cambridge
Summary:
Sodium channels are implicated in many serious conditions such as heart disease, epilepsy and pain, making them an important potential target for drug therapies. Unfortunately, there is still much scientists do not know about the molecules. New research provides fresh and unexpected insight into the structure of sodium channels and, specifically, one of its components -- -subunit molecules -- which are responsible for 'fine-tuning' the activity of the channel.

Sodium channels are implicated in many serious conditions such as heart disease, epilepsy and pain, making them an important potential target for drug therapies. Unfortunately, there is still much scientists do not know about the molecules. New Cambridge research provides fresh and unexpected insight into the structure of sodium channels and, specifically, one of its components -- β-subunit molecules -- which are responsible for 'fine-tuning' the activity of the channel. The research is published in the most recent edition of the Journal of Biological Chemistry.

Nerves and other electrically-excitable cells communicate with one another by transmitting electrical signals, and sodium channels play a vital role in this process. The sodium channel lies on the surface of the nerve and muscle cells and is composed of a large molecule called the α-subunit, together with smaller β-subunit molecules. The -subunits 'fine-tune' the activity of the channel, so that the initiation, frequency and duration of the action potential can be appropriately regulated. There are ten different forms of α-subunits and four different forms of -subunits. These are expressed in different types of cells and organs within the body.

The new Cambridge research was carried out by Sivakumar Namadurai and led by Dr Tony Jackson and Dr Dima Chirgadze from the University of Cambridge's Department of Biochemistry, and focussed on one of the -subunits, called β3. This molecule is particularly important in regulating sodium channels located on heart cells.

For the study, the researchers used a technique called protein X-ray crystallography to determine the atomic-resolution structure of a part of the 3-subunit called the 'immunoglobulin domain'. This region of the 3-subunit lies on the outside of the cell and binds to the heart sodium channel α-subunit.

They discovered that three 3-immunoglobulin domains come together to form a trimer (so-called because it is made up of three molecules). Using a technique called atomic force microscopy, Dilshan Balasuriya, led by Professor Mike Edwardson in Cambridge's Department of Pharmacology, imaged individual 3 trimers and confirmed that the complete 3-subunit trimers cross-linked up to three sodium channel α-subunits.

"Our results were unexpected," said Dr Jackson. "We have been working on the 3-subunit for about 14 years. In all that time, we have had to infer events at the molecular level indirectly. To actually see the atomic structure of the subunit and how it forms the trimer was one of those rare 'a-ha!' moments, like switching on a light bulb."

Dr Chirgadze added: "Our research has important implications for our understanding of the mechanism of sodium channel behaviour. Up until now there has been an assumption that individual sodium channels function independently. But this might be too simple a view. One very exciting possibility is that the cross-linking of sodium channel α-subunits by 3 trimers could lead to several sodium channels being functionally connected together. If correct, this would allow a more efficient initiation of the action potential."


Story Source:

The above story is based on materials provided by University of Cambridge. The original story is licensed under a Creative Commons Licence. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Namadurai, D. Balasuriya, R. Rajappa, M. Wiemhofer, K. Stott, J. Klingauf, J. M. Edwardson, D. Y. Chirgadze, A. P. Jackson. Crystal Structure and Molecular Imaging of the Nav Channel 3 Subunit Indicates a Trimeric Assembly. Journal of Biological Chemistry, 2014; 289 (15): 10797 DOI: 10.1074/jbc.M113.527994

Cite This Page:

University of Cambridge. "Structure of sodium channels different than previously believed." ScienceDaily. ScienceDaily, 17 April 2014. <www.sciencedaily.com/releases/2014/04/140417101159.htm>.
University of Cambridge. (2014, April 17). Structure of sodium channels different than previously believed. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/04/140417101159.htm
University of Cambridge. "Structure of sodium channels different than previously believed." ScienceDaily. www.sciencedaily.com/releases/2014/04/140417101159.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins