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Tiny changes are a big deal in human bodies. Understanding how our cells function is vital to understanding how our bodies work and how to prevent disease. It鈥檚 also incredibly challenging to study and measure anything at such a small scale.

Professor Erwin Neher is a German biophysicist who is very familiar with some of these challenges. In 1991, together with Bert Sakmann, he was for 鈥榙iscoveries concerning the function of single ion channels in cells鈥�. His contributions to biophysics also saw him admitted as a Corresponding Member of the 精东视频 in 2020.

But how did measuring channels in our cells鈥攎any with pores only the diameter of a single atom鈥攍ead to finding new treatments for diseases like cystic fibrosis, diabetes and epilepsy?

Logistics at the cellular level

Our cells are surrounded by membranes that separate the insides of a cell from its environment. In these membranes are passages called ion channels that allow a cell to communicate with its surroundings and can allow single atoms with electrical charges (ions) in and out.

You could think of each cell as a city surrounded by a border: it needs to make sure there are ways to transport goods and services in and out of its borders, and a way to regulate what鈥檚 coming in and what gets kept out.

Prior to Neher and Sakmann鈥檚 work in the 1970s, scientists knew this kind of communication between cells occurred, and that different ions were passing back and forth through the cell membrane, but they weren鈥檛 sure how. Neher wanted to prove the concept of ion channels by recording the electrical currents from those channels as they open and close. But there was a problem: at the time, there was no good way to measure electrical currents on such tiny scales within a time frame of a few millionths of a second.

Using a new technique of measurement called the 鈥榩atch clamp technique鈥�, they found a way to create a tight seal between a tiny glass tube (a pipette) and a cell membrane, allowing ions to move in or out of the pipette through an ion channel of the cell membrane. The pipette then forms part of an electric circuit, which allows the current to be measured. This technique made measurements highly specific, more reliable and easier to obtain than ever before.

Not only was Neher able to prove for the first time that specific ion channels existed, but the new measurement technique allowed scientists to study them in detail. Neher and Sakmann showed that, by analogy, cells had railways for trains, roads for vehicles and airport runways for planes to service the 鈥榗ity鈥�.

The scientists were also able to describe how all these comings and goings were regulated. Some ion channels have a specific 鈥榮ensor鈥� molecule that physically changes shape in a way that affects the passage of ions through the channel. Other ion channels have a pore only big enough (or small enough) to allow ions of a specific size to fit through. There may also be ring-shaped filters that will only let ions through if they鈥檙e positive, but not negative (or vice versa). In our city analogy, it鈥檚 why you can鈥檛 have a train entering the city via the road, or a car flying into the airport.

Small measurements, big impact

Neher鈥檚 work opened up brand new ways to treat a range of diseases by targeting treatments at specific ion channel functions. 鈥淔ollowing the development of the patch clamp, researchers worldwide adopted this technique for the study of diseases and drug action,鈥� he says. 鈥淎lthough I never did clinical work myself, this indirectly led to novel medications and improved therapies, which I am proud of.鈥�

The global impact of Neher鈥檚 discoveries is impressive for someone who only wanted to prove that ion channels existed. 鈥淥ur plan was just to prove the concept,鈥� says Neher. 鈥淗owever, it turned out that mutations in ion channels often lead to diseases like cystic fibrosis, so ion channel research became important for pharmacology.鈥�

鈥淭he laws of nature do not distinguish between countries and continents. The goal of science is to decipher these laws and scientists share their insights in this respect in a remarkable way.鈥�