Recombinant hTASK1 is an O(2)-sensitive K(+) channel.
Hypoxic inhibition of background K(+) channels is crucial to O(2) sensing by chemoreceptor tissues, but direct demonstration of O(2) sensitivity by any member of this K(+) channel family is lacking. HEK293 cells were transfected with a pcDNA3.1-hTASK1 construct; expression of hTASK1 was verified using RT-PCR and immunocytochemistry. Whole-cell K(+) currents of cells stably expressing hTASK-1 were, as anticipated, extremely sensitive to extracellular pH, within the physiological range (IC(50) approximately 7.0). All cells expressing this signature pH sensitivity were acutely modulated by pO(2); reduction of pO(2) from 150 to <40 mmHg (at pH 7.4) caused rapid and reversible suppression of pH-sensitive K(+) currents. Furthermore, these two regulatory signals clearly acted at the same channel, since the magnitude of the O(2)-sensitive current was dependent on the extracellular pH. These data represent the first direct verification that hTASK1 is O(2)-sensitive and reinforce the idea that this K(+) channel is key to O(2) sensing in chemoreceptors.
Lewis
A
A
School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom.
Hartness
M E
ME
Chapman
C G
CG
Fearon
I M
IM
Meadows
H J
HJ
Peers
C
C
Kemp
P J
PJ
D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D011994:Recombinant Proteins; C420132:potassium channel subfamily K member 3; D011188:Potassium; D010100:Oxygen