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

• Published in: Pflügers Archiv 2003-02, Vol.445 (5), p.577-583
• Main Authors: Morton, Michael J, O'Connell, Anthony D, Sivaprasadarao, Asipu, Hunter, Malcolm
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence - genetics; Animals; Biosensing Techniques; Electric Conductivity; Electrophysiology; Extracellular Space - metabolism; Female; Humans; Hydrogen-Ion Concentration; Mice; Molecular Sequence Data; Mutation - physiology; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Oocytes; Patch-Clamp Techniques; Potassium Channels - chemistry; Potassium Channels - genetics; Potassium Channels - physiology; Potassium Channels, Tandem Pore Domain; Protein Structure, Tertiary - physiology; Structure-Activity Relationship; Xenopus laevis
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-002-0901-2

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 Xenopusoocytes by two-electrode voltage clamp. Hydrogen ion block was independent of voltage with K(d) 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 K(d) 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