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ASIC1a ionic channels help bring mouse brain activity related seizure under control ( top ). The attacks channels mice lacking suffer more severe and prolonged ( down ).
Seimann et al., Nature Neuroscience , Advance Online Publication (June 8, 08)
Sometimes the crises become an endless nightmare. About 15% of epileptics will, at some point, experience status epilepticus, a medical emergency in which seizures can be stopped with powerful anesthetic. The researchers found a piece of cellular machinery - ion channel-- activated by an acid that helps bring the seizures under control. They hope the discovery will lead to new drugs that could stop these fatal events.
For decades, researchers have suspected a link between the brain acidity and seizures. In 1929, doctors noted that patients breathing CO2 had shorter crises; the gas increases the acidity of the blood from reaching the brain. Even without intervention, the brain pH may drop during a crisis due to changes in respiration and metabolism. John Wemmie, a psychiatrist at the University of Iowa in Iowa City and colleagues wondered if an ion channel called ASIC1a could play a role, as he is known to activate neurons by pumping calcium and sodium through the membrane cell when the brain becomes acidic.
team against normal mouse Wemmie with those that have been genetically modified to lack the channel. When they injected these knockout and controls with chemicals that cause seizures as normal mice did much better than those without ASIC1a. A compound called kainate produced serious convulsions of the whole body in the seven knockout mice, while six normal mice had only minor crises in their heads and forelimbs. A second KO group injected with another drug, PTZ, had longer crisis than control mice - and those seized were several times more likely to become fatal entire seizures brain tonic-clonic (formerly entered name "grand mal "). In contrast, mice genetically engineered to have twice the normal number of channels ASIC1A had shorter and less severe attacks than wild-type mice, reports online this week in team Nature Neuroscience .
Wemmie and his colleagues began studying whether ASIC1a also has a role in epileptic humans. If it does, Wemmie hope new drugs can help turn the channels on and stop seizures in patients who enter a bad state - possibly without the side effects of high doses of anticonvulsants currently available, which can also cause patients to stop breathing or experience kidney failure.
Jeffrey Noebels, a neurologist at Baylor College of Medicine in Houston, Texas, said a survey of status epilepticus is "good news," adding that the discovery may help clinicians understand why some people are more likely than others to experience the condition. Epileptologist Douglas Coulter of the University of Pennsylvania School of Medicine in Philadelphia acknowledges that the study is "convincing", but noted that much more work is needed to understand exactly how the channel exerts its beneficial effects.
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