Researchers prove there are no water molecules between the ions in the selectivity filter of potassium channels
Do potassium ions pass through the selectivity filter of a potassium channel alone or are there also water molecules between the ions? This issue has been a source of controversy for years. Adam Lange of the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin have now demonstrated that water molecules do not migrate together through the potassium channel. Since the experiments were first carried out on cell membranes under natural conditions, researchers have had solid evidence. Their work has just been published in the journal Science Advances.
Our cells need potassium ions to transmit nerve impulses and control heart rate, among other functions. Virtually all human cell membranes are equipped with potassium channels. Because potassium channels are of fundamental importance to biological processes and even the smallest changes can lead to serious diseases, tiny protein molecules are at the heart of research efforts around the world. In 2003, an American researcher was awarded the Nobel Prize in Chemistry for his elucidation of the structure of potassium channels.
Controversial debate on two different mechanisms
However, the question of how potassium actually passes through the canal to cross the cell membrane has not been clarified. For a long time, it was assumed that each potassium ion was followed by a water molecule and that the elements then aligned themselves, like links in a chain, and passed one after the other through the narrowest part of the potassium channel, the so-called selectivity filter. This was based on the fact that potassium ions are positively charged and would repel each other without the intermediate water molecules. However, this mechanism was challenged in 2014 by Göttingen researchers led by Professor Bert de Groot: Computer simulations have shown that there are no water molecules in the potassium channel selectivity filter. However, this did not end the debate. Subsequently, further studies were published that appeared to support the old mechanism and, apparently, refute the new one.
Today, researchers from the Berlin FMP have brought clarity to the debate: Carl Öster and Kitty Hendriks of Professor Adam Lange's research group and other colleagues from the FMP have used solid-state nuclear magnetic resonance (NMR) spectroscopy to show that potassium ions do migrate through potassium channels without intermediate water molecules. Their results show that potassium ions are positioned directly behind each other and push each other through the potassium channel from bottom to top.
"The technology we have used allows us to study membrane proteins in real cell membranes under natural conditions, for example, at room temperature or physiological salt concentrations," explains Kitty Hendriks. "Thus, we were able to show that under these conditions, there is no water between the potassium ions of the selectivity filter."
The first indications came from computer simulations and X-ray crystallographic data suggesting the absence of water molecules in the potassium channel selectivity filter. "However, these investigations were conducted under artificial conditions," explains Dr. Carl Öster. "With our additional data obtained by NMR spectroscopy, we now have a strong argument: the new mechanism is the right one."
Researchers at the FMP and their colleagues at the Max Planck Institute of Biophysical Chemistry led by Professor Bert de Groot, whose computer-assisted molecular dynamics simulations were also included in the study, have demonstrated that there are no water molecules between potassium ions.
"Five years ago, we would certainly not have been able to demonstrate this in this way, but we have now reached a point where we are able to effectively answer this important question," said Professor Adam Lange, leader of the research group that focuses on the study of membrane proteins, such as ion channels. He adds: "Since processes in potassium channels are fundamental to our health, our results have a great importance that goes beyond basic research.
