November 14, 2019

Blueprint for treating epilepsy

Structural details of a protein that is essential to normal brain function could improve treatments for epilepsy and other seizure disorders.

Proteins that move electrically charged ions of sodium, potassium and chloride across the cell membrane are vital for the control of cell volume — the amount of water inside the cell and regulation of intracellular chloride.

In central neurons, cation-chloride cotransporters, proteins that mediate the cotransport of sodium and/or potassium with chloride across the cell membrane, are essential to normal brain function. Genetically-induced abnormalities in ion transport can result in devastating seizures and death.

Eric Delpire, PhD, professor of Anesthesiology and Molecular Physiology & Biophysics, is an internationally known expert on the function of these proteins. Now, with colleagues at Zhejiang University School of Medicine in Hangzhou, China, he has determined the structure of the potassium-chloride cotransporter KCC1.

Their report, published in the Oct. 25 issue of Science magazine, sheds light on a potential ion transport mechanism for KCC1 and other KCCs and provides a blueprint for drug design that could lead to improved ways of treating epilepsy and other seizure disorders.

This research was supported in part by the National Institutes of Health (grants DK093501, DK110375) and by the Leducq Foundation.