The study revealed that structural and dynamic differences between selective and non-selective ion channels. In non-selective channels, the selectivity filter exhibits sizeable dynamics, which are not present in selective channels. The study was published in the journal Nature Communications.
The selectivity filter of non-selective ion channels can exist in two different forms. Dependent on the state of the selectivity filter, one or the other ion type may pass. Ion channels play prominent roles in organisms. During this signal transmission, charged atoms (ions) must enter and leave the involved cells. Ions cannot permeate lipophilic cell membranes.
Instead, they pass through protein channels in the cell membranes. In many cases, the ion channels allow the passage of only one specific ion type, i.e. they may be conductive for potassium but not for sodium ions or vice versa. The selectivity filter that is the narrowest part of the channel is responsible for this ion discrimination. Non-selective ion channels are very important in medicine.
Scientist Dr. Han Sun had examined system is a model system for several other non-selective ion channels in the human body. As she pointed out, physiologically and medically relevant in this context are the cyclic nucleotide-gated and hyperpolarization-activated cyclic nucleotide-gated channels (CNG and HCN channels): "We know that CNG channels are important for vision and smell. Dysfunctional HCN channels are implicated in various neurological diseases such as epilepsy or autism."
Specific Ions Prefer Specific Channel Structures
On their path to discovering how the non-selective NaK channel works, the scientists used a combination of nuclear magnetic resonance (NMR) spectroscopy and computer-assisted molecular dynamics simulations. The results revealed that the selectivity filter of the NaK channel dynamically changes between two structures.
Each structure is conductive for one of the two ion types. Dr. Han Sun reports: "Surprisingly, the computer simulations showed that potassium ions passing through the NaK channel prefer the structure of a potassium selective channel, while the mechanism of the sodium ion passage is similar to the passage of sodium ions through a sodium selective ion channel.
For further evidence for the crucial role of the dynamic structure of the NaK selectivity filter, the scientists experimented with a mutated NaK channel. This mutated NaK channel is conductive only for potassium ions. Professor Adam Lange gives an account of the results: "Our NMR investigations clearly revealed that the selectivity filter of this channel forms only a single structure."