Common mechanism underlies many diseases of excitability

Dec 28, 2009

Inherited mutations in voltage-gated sodium channels (Navs) are associated with many different human diseases, including genetic forms of epilepsy and chronic pain. Theodore Cummins and colleagues, at Indiana University School of Medicine, Indianapolis, have now determined the functional consequence of three such mutations.

As noted by Stephen Cannon and Bruce Bean, in an accompanying commentary, these results suggest that there might be a common mechanism for many channelopathies, diseases arising from mutations in ion channel genes such as those analyzed by Cummins and colleagues.

The authors studied the functional consequences of mutations in the human peripheral neuronal sodium channel Nav1.7, the human skeletal muscle sodium channel Nav1.4, and the human heart Nav1.5, which are associated with an extreme pain disorder, a muscle condition characterized by slow relaxation of the muscles, and a heart condition and , respectively.

Expression of these mutated proteins in a rat-derived dorsal root ganglion neuronal system led to the conclusion that the mutations all altered opening of the sodium channels such that the channels quickly reopened after an electrical impulse had been fired by the nerve cell causing a resurgent sodium current that triggered a second electrical impulse to be fired rapidly after the first.

These observations are consistent with the diseases all being characterized by excitability, over activity of that rely on electrical currents, such as , skeletal muscle cells, and heart muscle cells.

Explore further: Are my muscular dystrophy drugs working?

More information: www.jci.org/articles/view/4080… 5c50c65d9dc478d53b04

Provided by Journal of Clinical Investigation

5 /5 (1 vote)
add to favorites email to friend print save as pdf

Related Stories

Study: Why cold is such a pain

Jun 14, 2007

German scientists have identified a key molecule that helps animals feel pain associated with low temperatures.

New mechanism underlying pain found

Oct 16, 2006

Researchers at Johnson & Johnson Pharmaceutical Research & Development (J&JPRD) today announced that they have discovered a new molecular mechanism that may underlie neuropathic pain. The clearer understanding of the root-cause ...

Key finding in rare muscle disease

Jan 17, 2007

The finding is in the current issue of Annals of Neurology, a leading international neurology journal, in work led by Professor Nigel Laing and Dr Kristen Nowak of the Laboratory for Molecular Genetics at the Western Austra ...

Possible link between different forms of epilepsy found

Jun 16, 2008

Carnegie Mellon University neuroscientists have identified what may be the first known common denominator underlying inherited and sporadic epilepsy — a disruption in an ion channel called the BK channel. Although BK channels ...

Recommended for you

Are my muscular dystrophy drugs working?

1 hour ago

People with muscular dystrophy could one day assess the effectiveness of their medication with the help of a smartphone-linked device, a new study in mice suggests. The study used a new method to process ...

Cell death proteins key to fighting disease

12 hours ago

Melbourne researchers have uncovered key steps involved in programmed cell death, offering new targets for the treatment of diseases including lupus, cancers and neurodegenerative diseases.

Unlocking the secrets of pulmonary hypertension

Oct 30, 2014

A UAlberta team has discovered that a protein that plays a critical role in metabolism, the process by which the cell generates energy from foods, is important for the development of pulmonary hypertension, a deadly disease.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.