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Evolution and epilepsy
Date:1/21/2009

experienced recurrently. Epilepsy can begin at any age, but incidence is highest in the vulnerable first few weeks of life and remains elevated in later infancy and early childhood.

Initial work by the Penn team showed that the potassium and sodium channels were clustered together in small patches on the long fibers, called axons, which transmit electrical impulses between nerve cells. This raised several questions about the evolutionary and clinical underpinnings of this line of research: First, how did these two types of channels evolve to become so tightly paired at these patches on nerves? Second, is the development of these clusters over time important for understanding how channel mutations cause epilepsy? Third, clinically, since the potassium channel mutations linked to newborn epilepsy decreased channel activity, could drugs that increased the potassium channel activity be effective for seizure prevention?

Anchoring Sequences

Sodium and potassium channels are proteins embedded in the nerve membrane, with a part of each channel exposed to the cell's interior. In 2006, Cooper's team showed that the intracellular parts of the potassium and sodium channels possessed similar amino acid sequences. The shared sequences contained instructions specifying that the channels should be anchored together at spots along the axon.

They also found that these anchoring sequences were conserved in the potassium and sodium channels of vertebrates over 350 million years of evolution, from fish to humans. However, the channels of invertebrates, including fruit flies, worms, and squids, lacked the clustering sequences. In addition, some mutations causing epilepsy in infants prevented the channels from assuming their clustered positions within the patches.

"Finding that the sodium and potassium channel clustering required nearly identical sequences that seemed to have evolved at the same time was very surprising" said Coo
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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