Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells

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Abstract

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 pHo 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 ˜14 pS and ˜32 pS were recorded at a membrane potential of −60 mV. The K+ channels showed kinetic properties similar to TASK-1 (˜14 pS), TASK-3 (˜32 pS) and TASK-1/3 heteromer (˜32 pS). The presence of three TASK isoforms was tested by reducing [Mg2+]o 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 ˜0 mM also caused the appearance of ˜42 pS (TASK-1/3-like) and ˜74 pS (TASK-3-like) channels, in addition to the ˜14 pS (TASK-1-like) channel. The 42 pS channel was the most abundant, contributing ˜75% of the current produced by TASK-like channels. Ruthenium red (5 μM) had no effect on TASK-1 and TASK-1/3, but inhibited TASK-3 by 87%. In CB cells, ruthenium red caused ˜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 ˜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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