Scientists closer to solving epilepsy mystery

Jun 9 2008

Scientists in the United States believe they are a step closer to understanding why some people suffer from epileptic fits.

A multidisciplinary team of scientists used information from clinical observations made in the first half of the 20th century together with modern genetics and molecular biology to show that an acid-activated ion channel in the brain reacts to a drop in pH (increased acid) in a way that shuts down seizure activity.

For decades scientists have been grappling to resolve the mystery of epilepsy and now scientists from the University of Iowa and the Veterans Affairs Iowa City Health Care System believe they have found the key.

The link between low pH in the brain and stopping seizures was first implied almost 80 years ago when clinical experiments showed that breathing carbon dioxide, which makes brain tissue more acidic, helps stop epileptic seizures.

In experiments on mice, the scientists uncovered a channel known as ASIC1a, located on the surface of brain cells, which opens up in response to higher acid levels and admits charged atoms known as ions, this then activates other brain cells that block the seizures.

The researchers suspect that though ASIC1a does not appear to play a role in how a seizure starts, as the seizure continues and the pH is reduced, ASIC1a has a part in stopping further seizure activity.

ASIC1a's key role was revealed during experiments using genetically modified mice where the chemical kainate, known to trigger convulsions, was used on rodents that either had ASIC1a or had been modified to lack the ion channel.

The experiments showed that the ASIC1a-deprived mice had seizures that were severer and lasted longer.

Researcher Adam Ziemann says in the mice with ASIc1a, breathing CO2 caused brain pH to drop rapidly and protect mice from lethal fits - pH is a measure of acidity and the lower the pH index, the higher the acidity level.

The researchers say during seizures, ASIC1a appears to activate inhibitory neurons and this is the first research yet which demonstrates that inhibitory effect.

Though the research is promising the team warn that much more work must be done before the theory can be confirmed and a new therapeutic approach delivered.

The findings do present however the possibility of drugs which activate ASIC1a and switch off seizures.

Seizures involve the abnormal, synchronised firing of groups of neurons, which can cause physical symptoms such as spasms or convulsions and, in the most serious cases, altered control of vital bodily functions, such as breathing.

Approximately 2 to 4 percent of people will have a seizure at some point in their lives.... people who have epilepsy experience repeated seizures.

The vast majority of seizures stop by themselves, although in some cases, the fit develops into a highly dangerous condition called status epilepticus that has a mortality rate of up to 20 percent.

The study appears in the specialist journal Nature Neuroscience.