Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells
Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells
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DOI：
10.1113/jphysiol.2009.171181
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发表时间：
2009-06-15
影响因子：
5.5
通讯作者：
Carroll, John L.
中科院分区：
文献类型：
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作者：
Kim, Donghee;Cavanaugh, Eric J.;Carroll, John L.
大鼠颈动脉体（CB）血管球细胞表达TASK样背景K+通道，据信该通道在调节兴奋性和缺氧诱导的呼吸增加中发挥关键作用。在这里，我们研究了从大鼠CB细胞的单通道开口的动力学行为，以确定的“任务样”K+通道的分子身份。在由外向外的贴片中，CB细胞中的TASK样背景K+通道通过pH（o）从7.3降低至5.8而被抑制>90%。在浴和移液器溶液中含有140 mM KCl和1 mm Mg 2+的细胞附着贴片中，在-60 mV的膜电位下记录了两个主要开放水平，电导水平分别为14 pS和32 pS。K+通道显示出与ASK-1（类似于14 pS）、ASK-3（类似于32 pS）和ASK-1/3异聚体（类似于32 pS）相似的动力学性质。通过将[Mg 2 +]（0）降低至近似于0 mM来测试三种ASK同种型的存在，这对ASK-1的电导没有影响，但将ASK-1/3和ASK-3的电导分别增加至42 pS和74 pS。在CB细胞中，[Mg 2 +]（o）降低至接近0 mM也导致类似于42 pS（ASK-1/3样）和类似于74 pS（ASK-3样）通道的出现，除了类似于14 pS（ASK-1样）通道。42 pS通道是最丰富的，贡献了类似于75%的电流产生的任务样通道。钌红（5 μ M）对Task-1和Task-1/3没有影响，但对Task-3的抑制率为87%。在CB细胞中，钌红引起了类似于12%的TASK样活性抑制。Methanandamide使所有三种TASK的活性降低了80- 90%，CB细胞中的TASK样通道的活性也降低了约80%。在CB细胞中，缺氧引起了抑制的TASK-like通道，包括TASK-I/3-like通道。这些结果表明，在分离的CB细胞中，ASK-1、ASK-1/3和ASK-3均功能性表达，并且ASK-1/3异聚体提供了氧敏感性的ASK样背景K+电导的主要部分。
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.