Exploring the structure and function of an epilepsy-related ion channel

2023

Challenge

Ion channels are pores in the cell membrane that allow electrically charged atoms or molecules to pass in or out of a cell. These channels play a crucial role in regulating the electrical activity of nerve cells. The potassium channel Kv2.1 is particularly important in the mammalian brain, and mutations in the Kv2.1 gene can cause epilepsy in humans. Despite the importance of this ion channel, specific details of its structure remain to be investigated.

Advance

Ana Fernández-Mariño Ph.D., and Xiaofeng Tan, Ph.D., two research fellows in the lab of IRP senior investigator Kenton J. Swartz, Ph.D., led a groundbreaking study to characterize the Kv2.1 channel. They first determined the channel’ s detailed structure using cryogenic-electron microscopy, a technique that allows researchers to capture high-resolution images of sub-cellular structures. The team then introduced a series of Kv2.1 mutations previously linked to epilepsy into isolated fat cells to observe their impact on the channel’s structure and electrical function. These experiments identified a region inside the channel that plays an important role in its inactivation by epilepsy-causing genetic mutations.

Impact

These findings have important implications for understanding the origins of some forms of epilepsy, as well as how other ion channels similar to Kv2.1 can cease to function. They may also help scientists better understand the mechanisms of action for many treatments that affect Kv2.1 and similar channels.

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