Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K+ channel subunit, TASK-5, associated with the central auditory nervous system

Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K+ channel subunit, TASK-5, associated with the central auditory nervous system
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DOI:
10.1006/mcne.2001.1045
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发表时间:
2001-12-01
影响因子:
3.5
通讯作者:
Karschin, A
Karschin, A
中科院分区:
医学3区
文献类型:
--
作者:
Karschin, C;Wischmeyer, E;Karschin, A

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TWIK 相关的酸敏感 K+ (TASK) 通道有助于设定哺乳动物神经元的静息电位,最近被定义为细胞外质子和挥发性麻醉剂的分子靶标。我们从人类基因组文库中分离出了该亚家族的一个新成员 hTASK-5,并将其定位到染色体区域 20q12-20q13。 hTASK-5 在爪蟾卵母细胞中没有功能性表达,而包含 TASK-3 的 M1 和 M3 之间区域的嵌合 TASK-5/TASK-3 构建体产生 K+ 选择性电流。为了更好地将 TASK 亚基与神经元中的天然 K+ 电流关联起来,在大鼠大脑中阐明了所有 TASK 家族成员的精确细胞分布。全面的原位杂交分析表明,TASK-1 和 TASK-3 转录本在许多可能是胆碱能、血清素能或去甲肾上腺素能的神经元中表达最强。相反,TASK-5 表达见于嗅球二尖瓣细胞和浦肯野细胞,但主要与中枢听觉通路相关。因此,TASK-5 K+通道可能与辅助蛋白结合,在听觉系统中时间信息的传输中发挥作用。
TWIK-related acid-sensitive K+ (TASK) channels contribute to setting the resting potential of mammalian neurons and have recently been defined as molecular targets for extracellular protons and volatile anesthetics. We have isolated a novel member of this subfamily, hTASK-5, from a human genomic library and mapped it to chromosomal region 20q12-20q13. hTASK-5 did not functionally express in Xenopus oocytes, whereas chimeric TASK-5/TASK-3 constructs containing the region between M1 and M3 of TASK-3 produced K+ selective currents. To better correlate TASK subunits with native K+ currents in neurons the precise cellular distribution of all TASK family members was elucidated in rat brain. A comprehensive in situ hybridization analysis revealed that both TASK-1 and TASK-3 transcripts are most strongly expressed in many neurons likely to be cholinergic, serotonergic, or noradrenergic. In contrast, TASK-5 expression is found in olfactory bulb mitral cells and Purkinje cells, but predominantly associated with the central auditory pathway. Thus, TASK-5 K+ channels, possibly in conjunction with auxiliary proteins, may play a role in the transmission of temporal information in the auditory system.