Ion channel acts as powerful ‘brake’ after epileptic seizures

Published on December 19, 2012 at 1:39 PM · No Comments

Gene expression initiates protective electrical response

Given that epilepsy impacts more than 2 million Americans, there is a pressing need for new therapies to prevent this disabling neurological disorder. New findings from the neuroscience laboratory of Mark S. Shapiro, Ph.D., at The University of Texas Health Science Center at San Antonio, published Dec. 20 in the high-impact scientific journal, Neuron, may provide hope.

"A large fraction of epilepsy sufferers cannot take drugs for their disorder or the existing drugs do not manage it," said Dr. Shapiro, professor of physiology in the School of Medicine. "As a result, many opt for surgery to remove the hippocampus, a part of the brain where memories are stored but also where seizures are often localized. The heart-wrenching choice is between their memories and the epilepsy."

Genes go into action

A major finding of the study is that selected genes get switched on during and after a seizure, sending swarms of signals to reduce uncontrolled firing of nerve cells. A medication that amplifies this response after a person's initial seizure could thus prevent recurrent seizures and the onset of devastating epilepsy.

Uncontrolled electrical activity by specialized electricity-producing proteins in the brain called "ion channels" triggers epileptic seizures. One in 10 people have a lifetime risk of suffering a seizure, which can occur for a variety of reasons including traumatic brain injury, stroke or drug overdoses.

A powerful brake

Although not all seizures lead to epilepsy, some trigger changes in the brain that heighten the risk of the disorder. Dr. Shapiro's research sheds light on why most isolated seizures do not lead to full-blown epilepsy, whereas others do. An ion channel called the "M-channel" acts as a powerful "brake" on hyper-excitability in the brain. Another organizational protein, called AKAP79, acting much like an air-traffic controller, calls in more M channels as part of neuroprotective response machinery.

"In addition to epilepsy, the findings have implications for relief from chronic pains, cardiovascular disease and recovery from mood disorders," he added.

Pharmacological therapy to enhance M-channel gene expression or AKAP79 function "could jump-start this neuroprotective mechanism to prevent a seizure from turning into epilepsy," Dr. Shapiro said. "Administering it right after a traumatic brain injury could be very effective."

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