Determinants of pH sensing in the two-pore domain K+ channels TASK-1 and -2

TASK-1 and -2 are members of the two-pore domain potassium (K+) channel family and are sensitive to changes in extracellular pH. The effects of mutating charged, extracellular-facing residues in TASK-1 and –2 were studied in Xenopus oocytes by two-electrode voltage clamp. Hydrogen ion block was independent of voltage with Kd values of 149±17.9 nM [H+] (n=6) and 5.76±1.23 nM [H+] (n=7) for TASK-1 and -2, respectively. Compared to wild-type TASK-1, H72N, H98N, H98D and K210N displayed significant shifts in their Kd values for hydrogen ion block ([H+]; 110±9.80 nM, 737±170 nM, 321±85.9 nM and 267±9.92 nM, respectively, n=6 each, P<0.05). Although significantly reducing its pH sensitivity, mutation of H98 in TASK-1 did not abolish pH sensitivity; this implies that H98 is not the only residue or domain involved in pH sensing of TASK-1. TASK-2 does not possess a histidine residue at the homologous position. However, the inclusion of such a residue failed to produce the expected increase in pH sensitivity; instead, a slight decrease was observed. Despite their structural homology and common sensitivity to pH, the TASK family of K+ channels apparently has diverse pH-sensing mechanisms.