Novel insights into K(+) selectivity from high resolution structures of an open K(+) channel pore

K(+) channels are highly selective for K(+) over Na(+). Here we present several crystal structures of the MthK K(+) channel pore at up to 1.45 Å resolution. The MthK selectivity filter maintains a conductive conformation even in the absence of K(+), allowing the channel to conduct Na(+). The high resolution structures along with single channel recordings allow for an accurate analysis of how K(+) competes with Na(+) in a conductive selectivity filter. At high K(+) concentrations, two K(+) ions equivalently occupy the four sites in the selectivity filter while at low K(+)/high Na(+) a single K(+) ion remains bound in the selectivity filter, preferably at site 1 or 3. This single K(+) binding at low concentration effectively blocks the permeation of Na(+), providing a structural basis for the anomalous mole-fraction effect, a key property of multi-ion pores.