"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," Jegla explained. "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."
Managing this delicate rest-excitement balance are ion channels -- neuronal "gates" that control the flow of electrical signals between cells. While sodium and calcium channels help to excite neurons, potassium channels help to suppress signaling between cells, increasing the threshold at which nerves fire. However, the genetic mechanisms that control the potassium channels and set this threshold are not fully understood. Jegla's team focused on a particular potassium-channel gene -- called Kv12.2 -- that is active in resting nerve cells and is expressed in brain regions prone to seizure. "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," Jegla said. "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." Previous studies have suggested that the Kv12.2 potassium channel has a role in spatial memory, but Jegla and his team focused on how it might be related to seizure disorders.
In collaboration with Jeffrey Noebels at Baylor College of Medicine, the team used an electroencephalography (EEG) device to monitor the brains of mice. They found that mice missing the Kv12.2 gene did indeed have frequent seizures, albeit without convulsions. The team then stimulated mice with a chemical that induces convulsive seizures. They found that normal mice had a much higher convulsive-seizure threshold than mice with a defective Kv12.2 gene. The team also found the same results when they used a chemical inhibitor to block the Kv12.2 potassium channel in normal mice.
"In mice without a functioning Kv12.2 gene, nerve cells had abnormally low firing thresholds. Even small stimuli caused seizures," Jegla explained. "We think that this potassium channel plays a role in the brain's ability to remain 'quiet' and to respond selectively to strong stimuli."
Jegla hopes to open up new avenues of epilepsy research by studying whether activation of the Kv12.2 potassium channel in normal animals can block seizures. "Ion-channel defects have been identified in inherited seizure disorders, but many types of epilepsy don't have a genetic cause to begin with," Jegla explained. "They are often caused by environmental factors, such as a brain injury or a high fever. However, the most effective drugs used to treat epilepsy target ion channels. If we can learn more about how ion channels influence seizure thresholds, we should be able to develop better drugs with fewer side effects."
In addition to Jegla and Noebels, other scientists who contributed to this research include Xiaofei Zhang, Federica Bertaso, Karsten Baumgärtel, and Sinead M. Clancy of the Scripps Research Institute; Jong W. Yoo of the Baylor College of Medicine; and Van Lee, Cynthia Cienfuegos, Carly Wilmot, Jacqueline Avis, Truc Hunyh, Catherine Daguia, and Christian Schmedt of the Genomics Institute of the Novartis Research Foundation. This research was funded by the National Institutes of Health through its National Institute for Neurological Disorders and Stroke.
CONTACT Barbara Kennedy (PIO): 814-863-4682, email@example.com
Barbara K. Kennedy | EurekAlert!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy