Researchers in the United States said on Sunday they had found the key to a decades-old riddle over epileptic fits, helping to advance the quest for new treatments for this disabling condition.
Experiments in the last century found that by breathing carbon dioxide (CO2), an epileptic patient boosted acid levels in the brain and could terminate a fit, although the molecular switch for achieving this was veiled in mystery.
In experiments on mice, scientists from the University of Iowa and the Veterans Affairs Iowa City Health Care System, reporting in a specialist journal, believe they have found the switch.
A channel known as ASIC1a, located on the surface of brain cells, opens up in response to higher acid levels and admits charged atoms known as ions.
This in turn activates other brain cells that block the seizures, the investigators believe.
ASIC1a's linchpin role was uncovered thanks to experiments using genetically modified mice.
The researchers used kainate, a chemical known to trigger convulsions, on rodents that either had ASIC1a or had been modified to lack the ion channel. The ASIC1a-deprived mice had seizures that were severer and lasted longer.
"We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues and the pH is reduced, ASIC1a plays a role in stopping additional seizure activity," said investigator Adam Ziemann.
pH is a measure of acidity. The lower the pH index, the higher the acidity level.
Among mice with ASIc1a, breathing CO2 caused brain pH to drop rapidly and protect mice from lethal fits.
"In seizures, ASIC1a appears to be activating inhibitory neurons," said co-author John Wemmie, quoted in a University of Iowa press release.
"This is the first study to show that ASIC1a activation can have an inhibitory effect."
The findings are good news, because they offer up a tempting target for drugs to activate ASIC1a and switch off seizures, although the researchers caution that a lot more work lies ahead before such a theory is confirmed.
Seizures are unleashed by abnormal, synchronised firing of neuron groups, which results in disruption to the central nervous system, causing spasms and convulsions, and in the worst cases, stopping breathing.
Approximately two to four percent of people will have a seizure at some point in their lives, while for epileptics, the experience can be repeated many times.
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.