Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.
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.
Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK. helen_j_meadows@sbphrd.com
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HJ
Meadows
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Randall
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000143:Acids / Q000494:pharmacology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D002460:Cell Line; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D005905:Glyburide / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain; D011277:Pregnanediones / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014981:Xenopus
D000143:Acids; D017609:Barium Compounds; D002712:Chlorides; C498655:KCNK9 protein, human; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D011277:Pregnanediones; C024986:barium chloride; D005576:Colforsin; D002586:Cesium; D019789:Tetraethylammonium; C006477:alphaxalone; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D005905:Glyburide; D015056:1-Methyl-3-isobutylxanthine; D006221:Halothane; D002045:Bupivacaine