Almost all seizures naturally stop by themselves, the exceptions being episodes of status epilepticus. However the molecular mechanism that halts seizure activity is not understood. Researchers from the University of Iowa, USA, have now established that the acidity of brain cells, and how this changes during a seizure, plays a crucial role.

As neurons work, sending messages, they use up oxygen, glucose and energy, and produce carbon dioxide as waste. This is cleared naturally by the blood to be got rid of via the lungs. However if cells are working so hard the rate of clearance can't keep up with the rate of production, levels of carbon dioxide can build up. The presence of carbon dioxide makes cells more acidic.

Seizure activity is hard work for neurons, so their acidity rises during a seizure. Experiments 80 years ago showed that increasing the acidity of neurones could help stop seizures. Breathing carbon dioxide was also found to shorten seizures.

So how are acidity and seizures linked? It turns out that there is a type of ion channel in brain cells that is sensitive to acidity levels. Like other ion channels, it affects the excitability of brain cells (the ease with which they can be triggered to send signals, and hence the ease with which they can become over-excited into a seizure).

Dr Adam Ziemann and his colleagues theorised that as these channels, called ASIC1a, were opened by an increase in acidity, inhibition in the cells was increased and seizures stopped.

To test this, they studied seizures in mice with no ASIC1a channels because of a genetic defect, and compared them to seizures in mice with the normal gene. They found that the mice which had none of this type of acid-sensitive ion channels had seizures that were more severe and lasted longer than those of mice which had the channels. Another type of mouse with more than the usual number of ASIC1a channels had even shorter and milder seizures. However all these types of mouse had the same seizure threshold, showing that ASIC1a isn't involved in how seizures start, but in how they stop.

The researchers also measured the size of the change in acidity in brain cells caused by a seizure, and found that this was enough to open ASIC1a channels. Giving the mice air enriched with carbon dioxide to breathe produced an additional increase in acidity and protected against seizures.

This study, published in the journal Nature Neuroscience in July 2008, establishes the links between the acid-sensitive ion channel, brain acidity, carbon dioxide levels and seizures coming to an end naturally. Dr Ziemann and Professor John Wemmie, who led this work, concluded that the ion channels activate inhibitory neurons, which put a brake on signalling rates and bring seizures to a stop. Although the effect of breathing carbon dioxide on seizures has been known for decades, this is the first time it have been explained. The researchers speculated that a fault in the acid-sensitive system might lie behind status epilepticus.

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