Once open, roughly 10 million ions per second flow through each pore. To stop the flow of ions out of the channel, its poles probably rearrange at their crossing point, or smokehole, pinching off the lumen. At their most basic, these channels restore the membrane potential to its former strength after action potentials have reduced it. For years, Yellen has tried to find where in the channel its moving parts, or gates, lie and how they open and close in response to changes in the membrane potential. This is not a straightforward task in a large protein that comprises four subunits, each of which crisscrosses the membrane six times.
Scientists already know that ion channels are complex, able to open and close in different ways.
Some also feature a round peptide tethered to the interior end of the channel that can swing up and plug the channel from the inside. In previous work searching for such a gate, Yellen's team replaced amino acids facing the channel's inner pore with cysteine, which allowed the scientists to set up a chemical reaction along the channel's lumen that they could monitor through its effect on the current flow. Given that the reagent enters from the channel's interior side, all sites above the gate should become inaccessible once the gate closes. One of the Lasker Prize recipients, MacKinnon left HMS in 1996 for Rockefeller University in New York. The structure immediately became the working model for a field starved for direct structural information.