Extracellular Zn²⁺ accesses only the second H residue in K_Ca2.3 to cause moderate block. Representative whole cell currents of (A) K_Ca2.2 and (B) K_Ca2.3 channels evoked by voltage ramps from −80 to +80 mV under increasing concentrations of extracellular Zn²⁺. K_Ca2.3 current was more sensitive to block by Zn²⁺ than K_Ca2.2. (C) Representative currents of the mutant K_Ca2.2(N368H) showing an increased sensitivity to Zn²⁺ compared with K_Ca2.2. (D) Showing the reduced sensitivity to Zn²⁺ of the mutant K_Ca2.3(H522N), a mutation to mimic the K_Ca2.2 pore sequence that lacked the second H found in K_Ca2.3.