Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel

Neuropharmacology. 2001 Mar;40(4):551-9. doi: 10.1016/s0028-3908(00)00189-1.

Abstract

Human TASK-3 (hTASK-3) is a recently identified member of the two-pore domain potassium channel (2PDKC) family which in man is predominantly expressed in the cerebellum. Previous preliminary examination of this channel indicates that when expressed in Xenopus oocytes, it produces a K(+) selective background conductance and consequent shift in resting membrane potential, thus mimicking other 2PDKC. Here we describe some additional functional and pharmacological aspects of hTASK-3-mediated conductances expressed in both Xenopus oocytes and HEK293 cells. hTASK-3 expression produces steady-state currents that approximate Goldman--Hodgkin--Katz behaviour with respect to membrane potential. Despite this, voltage steps from -80 mV to potentials > approximately -20 mV induce currents that exhibit a clear time-dependent increase in current amplitude. Kinetically, this increase in current was well fit by a single exponential, the time constant of which was approximately 10 ms and appeared independent of test potential, between -20 and +80 mV. In HEK293 cells hTASK-3 currents were inhibited by extracellular acidosis with a mid-point for inhibition of pH 6.4. Furthermore, the activity of TASK-3 was potentiated by the volatile anaesthetic halothane but inhibited by the local anaesthetic bupivacaine.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Acids / pharmacology*
  • Animals
  • Barium Compounds / pharmacology
  • Bupivacaine / pharmacology
  • Cell Line
  • Cesium / pharmacology
  • Chlorides / pharmacology
  • Colforsin / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression
  • Glyburide / pharmacology
  • Halothane / pharmacology
  • Humans
  • Kinetics
  • Membrane Potentials / drug effects
  • Oocytes / drug effects
  • Oocytes / physiology
  • Potassium / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Tandem Pore Domain*
  • Pregnanediones / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tetraethylammonium / pharmacology
  • Time Factors
  • Xenopus

Substances

  • Acids
  • Barium Compounds
  • Chlorides
  • KCNK9 protein, human
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Pregnanediones
  • barium chloride
  • Colforsin
  • Cesium
  • Tetraethylammonium
  • alphaxalone
  • Tetradecanoylphorbol Acetate
  • Potassium
  • Glyburide
  • 1-Methyl-3-isobutylxanthine
  • Halothane
  • Bupivacaine