The effects of metal cations on the activation of recombinant human SK4 (also known as hIK1 or hKCa4) channels, expressed in HEK 293 cells, were tested using patch clamp recording. Of the nine metals tested, cobalt, iron, magnesium, and zinc did not activate the SK4 channels when applied, at concentrations up to 100 μM, to the inside of SK4 channel-expressing membrane patches. Barium, cadmium, calcium, lead, and strontium activated SK4 channels in a concentration-dependent manner. The rank order of potency was at Ca 2 + >Pb 2 + >Cd 2 + >Sr 2 + >Ba 2 + .