Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 587, Issue 12, Pages 2963-2975Publisher
WILEY-BLACKWELL
DOI: 10.1113/jphysiol.2009.171181
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Funding
- NIH [HL054621]
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Carotid body (CB) glomus cells from rat express a TASK-like background K+ channel that is believed to play a critical role in the regulation of excitability and hypoxia-induced increase in respiration. Here we studied the kinetic behaviour of single channel openings from rat CB cells to determine the molecular identity of the 'TASK-like' K+ channels. In outside-out patches, the TASK-like background K+ channel in CB cells was inhibited >90% by a reduction of pH(o) from 7.3 to 5.8. In cell-attached patches with 140 mM KCl and 1 mm Mg2+ in the bath and pipette solutions, two main open levels with conductance levels of similar to 14 pS and similar to 32 pS were recorded at a membrane potential of -60 mV. The K+ channels showed kinetic properties similar to TASK-1 (similar to 14 pS), TASK-3 (similar to 32 pS) and TASK-1/3 heteromer (similar to 32 pS). The presence of three TASK isoforms was tested by reducing [Mg2+](o) to similar to 0 mM, which had no effect on the conductance of TASK-1, but increased those of TASK-1/3 and TASK-3 to 42 pS and 74 pS, respectively. In CB cells, the reduction of [Mg2+](o) to similar to 0 mM also caused the appearance of similar to 42 pS (TASK-1/3-like) and similar to 74 pS (TASK-3-like) channels, in addition to the similar to 14 pS (TASK-1-like) channel. The 42 pS channel was the most abundant, contributing similar to 75% of the current produced by TASK-like channels. Ruthenium red (5 mu M) had no effect on TASK-1 and TASK-1/3, but inhibited TASK-3 by 87%. In CB cells, ruthenium red caused similar to 12% inhibition of TASK-like activity. Methanandamide reduced the activity of all three TASKs by 80-90%, and that of TASK-like channels in CB cell also by similar to 80%. In CB cells, hypoxia caused inhibition of TASK-like channels, including TASK-1/3-like channels. These results show that TASK-1, TASK-1/3 and TASK-3 are all functionally expressed in isolated CB cells, and that the TASK-1/3 heteromer provides the major part of the oxygen-sensitive TASK-like background K+ conductance.
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