System-specific O2 sensitivity of the tandem pore domain K+ channel TASK-1
Johnson, Rosalyn P., O'Kelly, Ita M. and Fearon, Ian M. (2004) System-specific O2 sensitivity of the tandem pore domain K+ channel TASK-1. American Journal of Physiology. Cell Physiology, 286, (2), C391-C397. (doi:10.1152/ajpcell.00401.2003).
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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
|Keywords:||hypoxia, background Kr channels, TASK-1, MAH cells|
|Divisions:||University Structure - Pre August 2011 > School of Medicine
|Date Deposited:||26 Nov 2008|
|Last Modified:||02 Mar 2012 12:51|
|Contributors:||Johnson, Rosalyn P. (Author)
O'Kelly, Ita M. (Author)
Fearon, Ian M. (Author)
|Contact Email Address:||I.M.O'Kelly@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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