Currents recorded were elicited by transfection of WT TASK-3, TASK-3-H98N or TASK-3-H98N-V221H into HEK-293 cells. Measurements were done in the whole-cell recording mode of the patch-clamp technique, using the voltage protocols in A (for currents shown in C, E and G) and B (for D, F and H). The intracellular solution contained 140 mM K+. Results in C and D correspond to TASK-3 (WT) and those in E and F and G and H to TASK-3-H98N and TASK-3-H98N-V221H respectively. In C, E and G the extracellular medium had 135 mM Na+ and 5 mM K+. In D, F and H, extracellular Na+ was replaced by an equimolar amount of K+. I, J and K show current-voltage relations for WT TASK-3and its mutants under the different extracellular K+ concentrations (circles 5 mM; triangles 140 mM). Results are means ± SEM. Number of experiments were respectively for 5 and 140 mM: 6 and 8 for WT TASK-3, 6 and 6 for TASK-3-H98N and 6 and 8 for TASK-3-H98N-V221H.