Navigation Links
Migraine mutations reveal clues to biological basis of disorder

Fifteen percent to 20 percent of people worldwide suffer from migraines excruciating headaches often presaged by dramatic sensations, or "auras." By studying a rare, inherited form of migraine, researchers at Vanderbilt University Medical Center have found clues to the biological basis of the painful, debilitating disorder.

In the Proceedings of the National Academy of Sciences, Alfred George Jr., M.D., and colleagues report that genetic mutations linked to this rare form of familial migraine alter the function of sodium channels protein "tunnels" through brain cell membranes involved in the electrical conduction of nerve impulses.

The findings identify cellular events that may prompt migraines specifically the aura that precedes them and suggest that medications targeting sodium channels might warrant a closer look as potential treatments for some forms of migraine.

George and colleagues investigated the physiological basis of a severe, inherited form of migraine called "familial hemiplegic migraine type-3" (FHM3). The aura associated with FHM3 often includes a transient weakness or paralysis of one side of the body.

FHM3 is caused by mutations in a sodium channel gene, SCN1A. Researchers in Europe had identified three mutations associated with the condition and contacted George about studying the cellular effects of these mutations.

"We were already studying this gene, SCN1A, in genetic forms of epilepsy," said George, the Grant W. Liddle Professor of Medicine, professor of Pharmacology, and the director of the Institute of Integrative Genomics. "This was a great opportunity to investigate the physiology of SCN1A mutants linked to another episodic neurological disorder."

George and colleagues genetically inserted the mutant sodium channels into cultured human cells and recorded the cells' electrical properties the key function modulated by sodium channels.

One mutant, called L1649Q, failed to generate any measurable current, indicating that this mutant caused a complete loss of function of the sodium channel.

The two other mutants L263V and Q1489K "work as sodium channels but are dysfunctional," George said. "They don't operate normally."

The mutations affected the opening and closing of the channel, a phenomenon known as "gating." Under normal situations, sodium channels are usually closed and open briefly to allow sodium to flow into the cell, which helps generate the electrical current conducted by the cell.

"These dysfunctional sodium channels tend to stay open too long, as if the gating mechanism is stuck," said George. "This problem may predispose neurons to fire more frequently."

The enhanced predisposition to nerve cell firing may be the spark that initiates the aura.

"The aura has been linked to a brain phenomenon known as 'cortical spreading depression,' which is essentially a wave of inexcitability that travels across the surface of the cortex (the brain's outer layer)," George explained.

"The dysfunctional channels probably aren't directly causing the headache. They're likely involved in causing cortical spreading depression, which then triggers other events ultimately culminating in the severe headache."

Although FHM3 is a rare form of migraine, the findings open up the possibility that more common types of migraine might involve dysfunctional sodium channels. George's team is continuing to study this in other cells and possibly in animal models.

The results also suggest a link between migraine and epilepsy, which often occur together.

"There's been evidence of some connection between migraine and epilepsy, but exactly how they're related is not clear," George said. "Now there's a gene involved in both. So maybe what we've learned here is that there can be a common genetic basis for epilepsy and migraine in some people."


Contact: Craig Boerner
Vanderbilt University Medical Center

Related medicine news :

1. Neuromuscular Dentistry Ends Womans Migraines
2. Migraine Tied to Thickening in Brain Area
3. Business Coalition Honors BlueChoice HealthPlan for Migraine Program
4. The HealthCentral Network Wins eHealthcare Awards for Breast Cancer and Migraine Web Sites
5. MAP Pharmaceuticals Reaches Agreement with FDA on Special Protocol Assessment for MAP0004 Phase 3 Clinical Trial in Patients With Migraine
6. Comatose locusts may help relieve migraines
7. Epilepsy Drug Doesnt Prevent Migraines
8. and Migraine Expert Teri Robert Announce Seventh Annual Migraine and Headache Poetry Contest
9. Migraines Frequency Influences Heart Attack, Stroke Risk
10. Overuse of Opioids, Barbiturates Boosts Chronic Migraine Risk
11. Skin Pain, Sensitivity Rises With Migraine
Post Your Comments:
(Date:11/25/2015)... ... November 25, 2015 , ... For the first time, Vitalalert ... Organizations, One Beat ” campaign. The partnership between the two groups began in 2014 ... MAP International’s cause. , MAP International was founded in 1954 and is an international ...
(Date:11/25/2015)... ... ... On November 25, 2015, officials of Narconon Arrowhead , the drug rehabilitation ... new cutting edge recovery program that has been 50 years in the making. ... with the purpose to free addicts from the symptoms and negative behaviors of addiction. ...
(Date:11/25/2015)... ... ... Smiles by Stevens is pleased to announce the addition of Botox® for ... aware of the benefits of Botox® in the treatment of moderate facial wrinkling, few ... and pain as a result of Jaw Tension, TMJ (temporo-mandibular joint) disorder, and Bruxism ...
(Date:11/25/2015)... ... November 25, 2015 , ... In an ongoing Clinical Study conducted by an ... IL, UV Angel is evaluating the efficacy of its product and its disinfection protocol. ... 30 beds) from May 2014 through October 2015 at a 360-bed, acute-care, academic medical ...
(Date:11/25/2015)... Spring, Md (PRWEB) , ... November 25, 2015 ... ... Pulmonary Hypertension Association (PHA) announces the nation’s Periwinkle Pioneers, individuals and groups responsible ... history of this disease. The Periwinkle Pioneers, nominated by the public, will receive ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... 2015 Kitov Pharma ceuticals ... a biopharmaceutical company focused on the development of therapeutic ... today announced the closing of its previously announced underwritten ... ), each representing 20 ordinary shares of the Company, ... ADSs and warrants were issued in a fixed combination ...
(Date:11/25/2015)...  Today AVACEN Medical announced the issue of United States patent No. ... ". This patent shields the company,s AVACEN 100 dry heat therapy medical device and specific methods ... Photo - ... ... ...
(Date:11/25/2015)... , Nov. 25, 2015 USP 800 ... drug preparations (e.g. pharmacists, pharmacy technicians, nurses, physicians, ... technicians). The chapter also covers all entities which ... pharmacies, hospitals, other healthcare institutions, patient treatment clinics, ... --> --> What is ...
Breaking Medicine Technology: