“…the selectivity filter) acting in concert with the opening of the inner helix bundle (Liu et al, 2001). Several pieces of evidence point to the selectivity filter as a region with a great deal of influence over the gating behaviour of K + channels, including the effect of certain permeant ions on gating (Demo and Yellen, 1992;Shapiro and DeCoursey, 1991;Spruce et al, 1989;Swenson and Armstrong, 1981), the effect of unnatural amino acid mutagenesis at the selectivity filter (Lu et al, 2001), and the role of subconducting states and specific P-loop mutants on single channel gating kinetics (Alagem et al, 2003;Chapman et al, 1997;Proks et al, 2001;Zheng and Sigworth, 1997). Gating of K + channels at the level of the selectivity filter has been traditionally associated with C-type inactivation, a slow process by which the channel enters a non-conductive conformation, and is sensitive to external K + concentration (Hoshi et al, 1991;Kiss et al, 1999;Liu et al, 1996;Lopez-Barneo et al, 1993).…”