Before reading this article, we advise that you read our background information about neuron structure and function.

Neurons relay information between the brain and the rest of the body in the form of electrical signals; and these are produced by the movement of potassium, sodium and calcium ions into and out of the neuron through structures known as ion channels. Once electrical activity reaches a certain threshold, the neuron 'fires' and the signal, known as an action potential, is conducted down its long arm (axon). Action potentials travel down a sequence of neurons to reach their destination, passing from the axon of one to the dendrites of another. The number of neurons traversed depends upon the distance the action potential must cover.

Epileptic seizures occur when neurons become over-excited and fire too many action potentials in rapid succession. Due to the role played by ion channels in generating action potentials, they are understandably the focus of a lot of research, looking at their normal activity and whether defects in their structure/function can cause seizures. Within each class of ion channel (sodium channels, potassium channels etc) there are many subgroups that operate in different ways; and so discovering how they all work is no small task.

Past studies have shown that, whilst sodium and calcium channels help to excite neurons (by opening and allowing their respective ions to pass through); potassium channels help to suppress signaling between neurons and increase the threshold at which neurons fire. This helps to prevent neurons from becoming over-excited (and from making each other over-excited), and stops them from firing too frequently (in response to the slightest of stimuli).

Scientists at Penn State University, Pennsylvania, and Baylor College of Medicine, Texas, recently investigated the genetic mechanisms that control potassium channels and determine the threshold of electrical activity at which neurons fire. They focused on the gene that encodes a potassium channel known as Kv12.2, because it is active both in resting nerve cells and in brain regions that are susceptible to seizure activity. According to previous studies the Kv12.2 channel plays a role in spatial memory, but this team was interested in how it relates to seizure disorders.

The group first used an electroencephalography (EEG) device to monitor the brains of two groups of animals. The first group was normal and healthy, whilst the other had been bred to lack the Kv12.2 gene (and so didn't produce any Kv12.2 potassium channels). The scientists found that the group missing the Kv12.2 gene had frequent, non-convulsive seizures.

Next, the team induced convulsive seizures in both groups, and discovered that normal subjects had a much higher convulsive-seizure threshold than those lacking the Kv12.2 gene. They then administered a chemical inhibitor to members of the 'normal' group, to block Kv12.2 potassium channels, and found that their convulsive seizure threshold decreased considerably (to a similar level as that seen in the group lacking the Kv12.2 gene).

Assistant Professor Timothy Jegla, Principal Investigator, Penn State University, commented on these findings:

"In mice without a functioning Kv12.2 gene, nerve cells had abnormally low firing thresholds. Even small stimuli caused seizures. We think that this potassium channel plays a role in the brain's ability to remain 'quiet' and to respond selectively to strong stimuli."

Many forms of epilepsy are caused by environmental factors (for example head injury or stroke), and amongst the genetic forms, a defective Kv12.2 gene is probably only present in a small proportion of people. The team hopes that the results of this study will lead to further investigations into whether activation of Kv12.2 potassium channels can block seizures induced in normal animals (representing seizures unrelated to a defective Kv12.2 gene). If the results are positive, drugs that target Kv12.2 channels could potentially be developed to increase seizure thresholds and treat some forms of epilepsy in the future.

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