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New molecular views of how neurons pace their signals

Communication between cells is a carefully coordinated matter. In the brain, for example, neurons talk by firing signals at a particular tempo, each impulse subsiding before the next arises. Their pacing relies on the activity of SK channels, molecules embedded in neurons’ outer membranes.

Toward the end of a signal, SK channels open to allow positively charged potassium ions to leak out of the cell, and the resulting electrical change delays subsequent signals. With new molecular structures, delineated at the resolution of atoms in Roderick MacKinnon’s Rockefeller lab and described recently in Science, scientists are now able to study in fine detail how these conduits function.

Using an advanced imaging technique known as cryo-electron microscopy, postdoc Chia-Hsueh Lee determined both the closed and open conformations of the human SK channel. He identified flexible sensors in a peripheral part of the channel that, in response to surges in calcium ions, initiate a chain of interactions that ultimately tugs its central pore open.

These findings could aid in the development of new therapies for diseases like Parkinson’s and hemolytic anemia, which have been linked to malfunctions in the channel.

portrait of Rod MacKinnon

Roderick MacKinnon
Investigator, Howard Hughes Medical Institute
John D. Rockefeller Jr. Professor
Laboratory of Molecular Neurobiology and Biophysics

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