System-specific O2 sensitivity of the tandem pore domain K+ channel TASK-1.
Hypoxic inhibition of TASK-1, a tandem pore domain background K+ channel, provides a critical link between reduced O2 levels and physiological responses in various cell types. Here, we examined the expression and O2 sensitivity of TASK-1 in immortalized adrenomedullary chromaffin (MAH) cells. In physiological (asymmetrical) K+ solutions, 3 microM anandamide or 300 microM Zn2+ inhibited a strongly pH-sensitive current. Under symmetrical K+ conditions, the anandamide- and Zn2+-sensitive K+ currents were voltage independent. These data demonstrate the functional expression of TASK-1, and cellular expression of this channel was confirmed by RT-PCR and Western blotting. At concentrations that selectively inhibit TASK-1, anandamide and Zn2+ were without effect on the magnitude of the O2-sensitive current or the hypoxic depolarization. Thus TASK-1 does not contribute to O2 sensing in MAH cells, demonstrating the failure of a known O2-sensitive K+ channel to respond to hypoxia in an O2-sensing cell. These data demonstrate that, ultimately, the sensitivity of a particular K+ channel to hypoxia is determined by the cell, and we propose that this is achieved by coupling distinct hypoxia signaling systems to individual channels. Importantly, these data also reiterate the indirect O2 sensitivity of TASK-1, which appears to require the presence of an intracellular mediator.
Johnson
Rosalyn P
RP
Department of Biology, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4K1.
O'Kelly
Ita M
IM
Fearon
Ian M
IM
D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D002461:Cell Line, Transformed; D019439:Chromaffin Cells / Q000378:metabolism; D063388:Endocannabinoids; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012996:Solutions; D015032:Zinc / Q000494:pharmacology
D001095:Arachidonic Acids; D063388:Endocannabinoids; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D012996:Solutions; C420132:potassium channel subfamily K member 3; D015032:Zinc; D011188:Potassium; D010100:Oxygen; C078814:anandamide