Chicago—Have you thanked a voltage-gated potassium channel today?
These channels are ubiquitous across excitable cells like nerve and muscle cells, where they open and close to facilitate the flow of positively charged potassium ions across a membrane. In doing so, they’re a vital part of the processes behind thought and motion, like being able to read this piece.
But according to Benoît Roux, a professor of chemistry at the University of Chicago, the exact mechanics of how these potassium channels open and close have been mysterious because most of the research on the channels has been done on their active, or open, state. Scientists have less insight into what the transitional stages between fully open and fully closed even look like.
On Monday, during a talk in the Division of Biochemistry and Chemical Biology at ACS Fall 2026, Roux presented new research that sheds light on those very transition states that the channels pass through when they open and close. Roux uploaded a paper before peer review to the bioRxiv server in January, which also outlines the work (DOI: 10.1101/2025.11.13.687653).
Roux described how his team used a mutant version of a potassium channel and generated a cryo-electron microscopy (cryo-EM) structure of it. Previously, it had been thought that activating the voltage-sensing domain (VSD) of the channel mechanically opened the gate. But the mutant version of the channel made it easier to distinguish between when the VSD is activated and when the channel actually opens. The new structure shows a previously uncharacterized transitional state with an activated VSD, but with the channel remaining closed.
Roux said this likely means that activating the VSD does not mechanically open the gate. “What we see is more like something a bit more subtle and more dynamic,” he said. It’s still not completely clear, but he suggests that opening the gate may have more to do with changing its open-closed equilibrium.
With the ubiquity of these channels, Roux said that knowing how they work is critical to potentially targeting them with drugs. “These days, we can’t afford to be in the dark,” he said. “We have to understand the mechanism.”
