Old Gene Family Underlying Epilepsy Found

Scientists at the Pennsylvania State University (Penn State) made a discovery that could inform future therapies aimed at treating epilepsy. An investigations team determined that the excessive firing of neurons inside the human brain is being controlled by a family of genes that has ancient roots, and which has been involved in producing the condition known as epilepsy for thousands of years. The genes found in the new study are essential towards controlling the way nerve cells fire in the brain, e! Science News reports.

The new investigation was conducted by Penn State assistant professor of biology Timothy Jegla. The expert and his team thus managed to gain new knowledge into the factors that underlie the development of epilepsy. “In healthy people, nerves do not fire excessively in response to small stimuli. This function allows us to focus on what really matters. Nerve cells maintain a threshold between rest and excitement, and a stimulus has to cross this threshold to cause the nerve cells to fire. However, when this threshold is set too low, neurons can become hyperactive and fire in synchrony. As excessive firing spreads across the brain, the result is an epileptic seizure,” the team leader says.

The delicate balance that exists between neurons' rest-excitement states is mediated by neuronal “gates” known as ion channels. These structures control the way electrical signals are passed through cells. These signals represent the main method neurons use to communicate with each other. Information is transmitted from one nerve cell to the other via differences in the potential of neural membranes. Once the electrical signal reaches a synapse, neurotransmitters are sent from the first neuron to the second, thus producing the same difference in electrical potential in the second neuron. The electrical signal is therefore passed on from one neuron to the other.

While analyzing ion channels, Jegla and his team decided to focus their attention on the potassium-channel gene Kv12.2, which is expressed more heavily in areas of the brain that are prone to epileptic seizures. “We decided that Kv12.2 was a good candidate for study because it is part of an old gene family that has been conserved throughout animal evolution. This ancient gene family probably first appeared in the genomes of sea-dwelling creatures prior to the Cambrian era about 542-million years ago. It is still with us and doing something very important in present-day animals,” the team leader says.

“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,” the expert concludes.