Famously picky, potassium channels usher K+ ions across cell membranes while excluding smaller Na+ ions. The key to the choosiness is the channel's selectivity filter, a glycine-lined tunnel through which desolvated ions must pass single file. To probe the chemical basis of the filter's function, Tom W. Muir and Roderick MacKinnon of Rockefeller University, New York City, and their coworkers have now synthesized a potassium channel with D-alanine in place of one of the filter's glycine residues (Science 2006, 314, 1004). Although the native channel's filter adopts a K+-conductive structure only when K+ is present, the semisynthetic channel maintains the K+-conductive structure when K+ concentrations are vanishingly low and even when Na+ is present. As a consequence, the semisynthetic channel retains the native channel's characteristic K+ selectivity when both ions are present but conducts Na+ in the absence of K+. The researchers conclude that potassium channel selectivity depends not only on the filter's previously established preference for hosting multiple K+ ions at one time but also on the channel's ability to adapt its structure differently to K+ and Na+.