Dynamic channels: NMR tracks the ions

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  • Published: Mar 1, 2018
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Dynamic channels: NMR tracks the ions

Selective filtering

Computer simulation of the NaK channel. The channel (yellow and orange) enables the flow of ions across the cell membrane. Credit: Barth van Rossu

Researchers in Germany have demonstrated using nuclear magnetic resonance (NMR) spectroscopy how the selectivity filter of the cell membrane's NaK protein ion channel forms only a single structure to control the flow of potassium ions.

The proteins that comprise the channels in the body's cell membranes are highly selective, they transport only those components with which they have evolved to function. One channel will transport potassium ions, for instance, but will not carry sodium ions despite their similarities. However, there are ion channels that can modulate the flow of two kinds of ions. How this is achieved has remained something of a mystery. Now, NMR work underpinned by and computer-assisted molecular dynamics simulations carried out by a team of scientists led by Adam Lange at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Goettingen, Germany, and colleagues in China, believe they have solved the mystery.

The team has shown that there are structural and dynamic differences between selective and non-selective ion channels. Writing in the journal Nature Communications, the team explains how for non-selective channels, a selectivity filter exhibits considerable dynamics, which are not seen in the selective channels. This selectivity filter has two forms which are switched depending on cellular requirements which will allow one or the other ion type to pass under specific conditions.

Stimulating science

Ion channels are present in all animals. They allow stimuli to be recognized and information passed to the brain through electrochemical signals. Polar ions cannot permeate lipophilic cell membranes and it is the openings in these proteins that allow them to be transported in and out of the cell. The selectivity filter at the heart of such ion channels is the narrowest part of the channel itself and allows for ion discrimination. However, when it comes to the NaK channel, which can transport both sodium and potassium ions, there is a problem. How can it modulate the flow of each type of individually when it allows both to pass through? The new NMR insights offers an explanation that could assist in the development of novel treatments for various diseases.

"While X-ray crystallographic images showed us the three-dimensional structure of the channel, it was difficult to explain why this channel is conductive to two different ion types with similarly high efficiency," explains Lange. "This was particularly hard to understand because the sequence and the three-dimensional structure of the selectivity filter are similar to the ones in potassium selective channels."

NaK, OK

Colleague Han Sun points out that this particular ion channel can be seen as a model system for several other non-selective ion channels in the human body. She explains that there are numerous physiologically and medically relevant ion channels, such as 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," Sun says. "Dysfunctional HCN channels are implicated in various neurological diseases such as epilepsy or autism."

"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," Sun adds. Until now, researchers believed that the structure of the selectivity filter is the same for sodium and potassium ion transport through the NaK channel.

Related Links

Nature Commun 2018, online: "A single NaK channel conformation is not enough for non-selective ion conduction"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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