Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Discovery of New Structure of Cell’s Communication Channel Could Aid Drug Development

Published: Wednesday, April 30, 2014
Last Updated: Wednesday, April 30, 2014
Bookmark and Share
Researchers hope discovery will lead to improvements in drugs that act on the sodium channel to treat a range of cardiac and pain conditions.

The structure of sodium channels – which play an essential role in the functioning of heart and nerve cells – are different than previously believed. 

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 b-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 b-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 b-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 b3-subunit called the ‘immunoglobulin domain’. This region of the b3-subunit lies on the outside of the cell and binds to the heart sodium channel α-subunit.

They discovered that three b3-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 b3 trimers and confirmed that the complete b3-subunit trimers cross-linked up to three sodium channel α-subunits.

“Our results were unexpected,” said Dr Jackson. “We have been working on the b3-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 b3 trimers could lead to several sodium channels being functionally connected together. If correct, this would allow a more efficient initiation of the action potential.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,700+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Greater Understanding Of Polycystic Ovary Syndrome
A new genetic study of over 200,000 women reveals the underlying mechanisms of polycystic ovary syndrome, as well as potential interventions.
Wednesday, September 30, 2015
Maintaining Healthy DNA Delays Menopause
An international study of nearly 70,000 women has identified more than forty regions of the human genome that are involved in governing at what age a woman goes through menopause.
Tuesday, September 29, 2015
New Consortium to Develop and Study Early Stage Drugs
An innovative new Consortium will act as a ‘match-making’ service between pharmaceutical companies and researchers in Cambridge with the aim of developing and studying precision medicines for some of the most globally devastating diseases.
Thursday, July 30, 2015
MRSA Contamination Found in Supermarket Pork
A survey carried out earlier this year has found the first evidence of the ‘superbug’ bacteria Methicillin-Resistant Staphylococcus Aureus (MRSA) in sausages and minced pork obtained from supermarkets in the UK.
Monday, June 22, 2015
Expression of Certain Genes Changes with the Seasons
As the seasons change, so do the expression levels of many human genes, including ones involved in immune function, according to new research.
Thursday, May 14, 2015
Blood Markers Could Help Predict Outcome Of Infant Heart Surgery
New research suggests it may be possible to predict an infant’s progress following surgery for congenital heart disease by analysing a number of important small molecules in the blood.
Friday, May 08, 2015
Poisons, Plants and Palaeolithic Hunters
Dr Valentina Borgia to develop a technique for detecting residues of deadly substances on archaeological objects.
Saturday, April 11, 2015
‘Mini-Lungs’ Grown To Aid The Study Of Cystic Fibrosis
'Mini-lungs’ have been created using stem cells derived from skin cells of patients with cystic fibrosis.
Thursday, March 19, 2015
Gene Discovery Provides Clues To How TB May Evade The Immune System
The largest genetic study of TB susceptibility to date has led to a potentially important new insight into how the pathogen manages to evade the immune system.
Tuesday, March 17, 2015
Human Genome Includes 'Foreign' Genes Not From Our Ancestors
Many animals, including humans, acquired essential ‘foreign’ genes from microorganisms co-habiting their environment in ancient times, according to research published in the open access journal Genome Biology.
Monday, March 16, 2015
Order Matters: Sequence Of Genetic Mutations Determines How Cancer Behaves
The order in which genetic mutations are acquired determines how an individual cancer behaves, according to research from the University of Cambridge, published today in the New England Journal of Medicine.
Thursday, February 12, 2015
Artificially-intelligent Robot Scientist ‘Eve’ Could Boost Search for New Drugs
Eve, an artificially-intelligent ‘robot scientist’ could make drug discovery faster and much cheaper, say researchers writing in the Royal Society journal Interface.
Wednesday, February 04, 2015
Using Genome Sequencing to Track MRSA in Under-resourced Hospitals
Whole genome sequencing of MRSA from a hospital in Asia has demonstrated patterns of transmission in a resource-limited setting, where formal screening procedures are not feasible.
Thursday, December 11, 2014
Amazing Feet Of Science: Researchers Sequence The Centipede Genome
What it lacks in genes, it certainly makes up for in legs: the genome of the humble centipede has been found to have around 15,000 genes – around 7,000 fewer than a human.
Wednesday, November 26, 2014
Molecular Event Mapping Opens Door to more in silico Tests
It is hoped that this new approach to mapping and predicting the impact of chemical compounds in the body could reduce the need for toxicity tests in animals.
Wednesday, November 19, 2014
Scientific News
Breaking Through the Barriers to Lab Innovation
Here we examine the drivers behind the move for greater innovation, the challenges and current trends in laboratory informatics, and the tools that can be used to break these barriers.
Education and Expense: The Barriers to Mass Spectrometry in Clinical Laboratories?
Here we examine the perceived barriers to mass spec in clinical laboratories and explore the possible drivers behind the recent shift in uptake of the technology in clinical settings.
Fruit Fly Pheromone Flags Great Real Estate for Starting a Family
Finding could aid efforts to control mosquito-borne diseases like malaria by manipulating odorants
Gene Editing Could Enable Pig-To-Human Organ Transplant
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Antioxidants Cause Malignant Melanoma to Metastasize Faster
Fresh research at Sahlgrenska Academy has found that antioxidants can double the rate of melanoma metastasis in mice.
New Therapy Reduces Symptoms of Inherited Enzyme Deficiency
A phase three clinical trial of a new enzyme replacement medication, sebelipase alfa, showed a reduction in multiple disease-related symptoms in children and adults with lysosomal acid lipase deficiency, an inherited enzyme deficiency that can result in scarring of the liver and high cholesterol.
Adult High Blood Pressure Risk Identifiable in Childhood
Groups of people at risk of having high blood pressure and other related health issues by age 38 can be identified in childhood, new University of Otago research suggests.
Analyzing Protein Structures in Their Native Environment
Enhanced-sensitivity NMR could reveal new clues to how proteins fold.
Supercoiled DNA is Far More Dynamic Than the “Watson-Crick” Double Helix
Researchers have imaged in unprecedented detail the three-dimensional structure of supercoiled DNA, revealing that its shape is much more dynamic than the well-known double helix.
Mini-kidneys Successfully Grown from Stem Cells
Researchers from Murdoch Childrens Research Institute have perfected a method of turning stem cells into mini-kidneys for use in drug screening, disease modelling and cell therapy.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos