Cover picture: Coupling of the S4 voltage sensor to C-type inactivation in the K+ channel (Kv 1.2-2.1): the “four-legged runner” model. As the transmembrane S4 segment moves outward, its R293 residue contacts F344 in S5, starting a conformational wave that propagates to the pore region and destabilizes it. Destabilization predisposes to C-type inactivation by allowing dilation of the outermost K+-binding site, thus destroying its ability to complex and conduct K+ ions (see Viewpoint by Hoshi and Armstrong, 151–160).
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