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Heteromeric TASK‐1/TASK‐3 is the major oxygen‐sensitive background K + channel in rat carotid body glomus cells
Author(s) -
Kim Donghee,
Cavanaugh Eric J.,
Kim Insook,
Carroll John L.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.171181
Subject(s) - carotid body , glomus cell , biophysics , chemistry , conductance , membrane potential , anatomy , biochemistry , biology , electrophysiology , neuroscience , mathematics , combinatorics
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 m m KCl and 1 m m Mg 2+ 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 [Mg 2+ ] o to ∼0 m m , 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 [Mg 2+ ] o to ∼0 m m 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 μ m ) 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.