At first, Erwin Neher didn’t realize what he was looking at. He and his colleague Bert Sakmann—who occupied adjoining labs at the Max Planck Institute for Biophysical Chemistry in Göttingen starting in the 1970s—had been trying to perfect a technique for watching individual ion channels do their thing. Working with isolated frog muscles and an oscilloscope, the pair had already seen what appeared to be the signature trace of channel proteins flickering open in response to the neurotransmitter acetylcholine. But the signal was anything but clean.
“With these single-channel recordings, the thing you’re always fighting is noise,” says Yale’s Fred Sigworth, who had just joined Neher’s lab as a postdoc. “So you’d approach the cell with your pipette and you’d see this very noisy current”—a reflection of the thermal motion of ions in the vicinity of the pipette tip. As a result, the channel openings they’d witnessed to that point ...