'Paradigm shift' explains potassium channels
A new discovery is being described as a 'paradigm shift' in understanding how ions pass through cell walls.
Researchers at the University of Dundee, the Max Planck Institute for Biophysical Chemistry, the University of Göttingen and the University of Oxford have observed how ion permeate through potassium channels and the process does not follow previous predictions.
They have published their research in the journal Science.
Potassium channels are tiny pores that stud the surface of almost all cell types in the human body. The channels aid transmission of signals between brain cells as well as help control the frequency of our heartbeats.
When these channels are not working properly, they are implicated in a range of diseases of the heart and of the neurodegenerative system.
These pores allow potassium ions to pass through the cell wall using extremely rapid-fire 'open and close gates', acting as a highly efficient filtration system.
A previous theory in ion trasmission led to American biochemist Roderick MacKinnon receiving the 2003 Nobel Prize in Chemistry. MacKinnon proposed that ions were separated by water as they passed through these channels and that ion-to-ion contact was unlikely due to high electrostatic repulsion.
MacKinnon's previous research was limited to examining the potassium channels by looking at static or `closed-state' crystal structures. Advances in computing now allow researchers to now look at these channels 'in action' and with much more detail. Therefore, the new research has found a completely different scenario, using advances in technology that reveal fundamental physical principles in potassium channels' operation which here to fore could not be seen.
Computer simulations at the atomic level — including transmembrane voltage — found that water is not transported through potassium channels along with ions, nor is needed to separate potassium ions. Instead, pairs of potassium ions are stably formed and pass through potassium channels with startling efficiency, driven by electrostatic repulsion.
"Our findings explain how potassium flux is able to happen at the maximum physically attainable speed, vital to the fast response of neurons.
"This is a paradigm shift in the field. It changes our understanding of how these hugely important channels work. These channels are tremendously important as they are active in all cells — so it is vital that we understand how they work."
Dr Ulrich Zachariae, Reader in Computational Biophysics and Drug Discovery, the University of Dundee.
Potassium channels selectively conduct K+ ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K+ concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K+ ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K+ conduction. Crystallographic data are consistent with directly neighboring K+ ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K+ channels.
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