Activation of certain acid-sensing molecules in the brain can interrupt severe seizures associated with epilepsy, reports a study published online in Nature Neuroscience this week. This could aid in the development of drugs to target epilepsy, a condition that can often be very difficult to treat.
Epileptic seizures can be interrupted by breathing air with elevated levels of carbon dioxide. This additional carbon dioxide acidifies the brain, but it is not yet known how increased acidity stops the increased firing of nerve cells that causes a seizure. John Wemmie and colleagues suggest that a class of acid-sensitive channels in nerve cell membranes, the ASIC channels, might be involved.
To test their hypothesis, the scientists induced seizures in mice lacking the channel molecule ASIC1a. These mice suffered more severe convulsions and died more often from seizures than normal mice treated the same way. While carbon dioxide inhalation helped stop seizures in normal mice, it had no effect on seizures in mice lacking ASIC1a. The scientists also observed that inhibitory nerve cells were particularly enriched for ASIC1a, and were strongly activated in an acidic environment.
These results might explain how acidity stops seizures, and suggest that ASIC1a might be a promising target for epilepsy drug development.