The implications of the results from this paper are extensive - opening up further questions and potential studies about the workings of K⁺ channels. K⁺channels themselves are found vastly throughout organisms, driving the action potential in neurons and hormonal signalling making it one of, if not the most, abundant ion channel.

Do all K⁺ channels have the same degree of specificity for K⁺? Is this specificity maintained throughout all classes and species?

The comparisons throughout the paper to the model K⁺ system KcsA brings into disrepute that selectivity of K⁺ over Na⁺ is mediated by the same mechanism - despite the conserved TVGYG sequence. In KcsA, it was discovered that the slightly larger size of the K⁺ ion (compared to Na⁺) was required in order to keep the pore in an open conformation via the selectivity filter. This, however, is not the case in MthK. The consequence of this is that selectivity across a whole range of K⁺ pores could be mediated by a range of different ways - food for thought for many.

Whilst studies had suggested previously that K⁺ ions bind in the filter at alternate sites in KcsA, with such high resolution structures achieved via X-Ray Crystallography and complementary 1D electron density, this property can now be regarded as a certainty.
The such high resolution structure is said by the authors to be "a first-time structural perspective" of what is termed the anomalous mole-fraction effect. It is believed that preference for K⁺ in an environment containing Na⁺ is maintained as the smaller Na⁺ ion does not carry enough charge to repulse an ion across the pore.

This is best described by the following diagram:






In a K⁺ only environment, two K⁺ will occupy the pore (in this case at positions 2 and 4). Upon entry of a 3rd K⁺ ion to the edge of the pore, the stabilisation between the pore and ions is weakened by the repulsion of charge between the ions. This pushes one ion out of the pore.










The pore is once again occupied by two K⁺ ions and is reset awaiting the repulsion of a further K⁺ ion












In the mixed K⁺/Na⁺ environment, ions are more likely to bind in positions 1 and 3. Upon the binding of Na⁺ to position 1, there is not sufficient repulsion to eject a K⁺ out of the exit. It is, therefore replaced by a K⁺ ion at position 1.








Positions 1 and 3 are now occupied by K⁺ ions and upon the collision of a further K⁺ ion into the pore entrance, repulsion will cause ejection and shifting of the ions within the selectivity filter.









Summary

The paper, therefore, concludes that the method by which the MthK K⁺ channel pore is selective of K⁺ over Na⁺ even in the presence of both ions is via the mechanism above. This is of marked difference to that of the model system KcsA and whilst, as explained, the amino acid sequence involved in the filter is homologous, these organisms have evolved different mechanisms for selectivity.

In addition, the authors showed that MthK channel is able to retain a conductive conformation in the absence of K⁺, unlike the prototypic channel KcsA.