The role of pH-sensitive TASK channels in central respiratory chemoreception.
The role of pH-sensitive TASK channels in central respiratory chemoreception.
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DOI：
10.1007/s00424-014-1633-9
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Guyenet PG
中科院分区：
文献类型：
--
作者：
Bayliss DA;Barhanin J;Gestreau C;Guyenet PG
K2P背景K+通道家族中的许多亚基对生理范围内细胞外pH的变化很敏感，这使得它们可能介导各种pH依赖性过程。基于几个被认为在CO2/H+呼吸调节中起作用的脑干神经元细胞群的表达模式，三个TASK亚基- TASK-1， TASK-2和TASK-3 -被特别假设参与了这种中枢呼吸化学反射。对于酸敏感的TASK-1和TASK-3通道，尽管它们在脑干呼吸控制系统（包括假定的化学受体群体）的多个水平上广泛表达，但在基因敲除小鼠中进行的实验没有提供它们参与二氧化碳呼吸调节的证据。相比之下，碱激活的TASK-2通道在脑干的分布更受限制，并且定位于后梯形核（RTN）中表达phox2b的化学受体神经元。值得注意的是，在以中枢呼吸化学敏感性降低为特征的先天性中枢低通气综合征（CCHS）的Phox2b27Ala/+小鼠遗传模型中，选择性消融表达phox2b的RTN神经元伴随着相应的TASK-2表达缺失。此外，基因缺失TASK-2在体外降低了RTN神经元的pH敏感性，降低了原位碱诱导的呼吸网络抑制，降低了体内对CO2/H+的通气反应。值得注意的是，来自TASK-2−/−小鼠的RTN神经元亚群保留了其pH敏感性，至少部分原因是残留的pH敏感背景K+电流，这表明RTN神经元pH敏感性的其他机制（可能还有其他K2P通道）尚未确定。
A number of the subunits within the family of K2P background K+ channels are sensitive to changes in extracellular pH in the physiological range, making them likely candidates to mediate various pH-dependent processes. Based on expression patterns within several brainstem neuronal cell groups that are believed to function in CO2/H+ regulation of breathing, three TASK subunits – TASK-1, TASK-2 and TASK-3 – were specifically hypothesized to contribute to this central respiratory chemoreflex. For the acid-sensitive TASK-1 and TASK-3 channels, despite widespread expression at multiple levels within the brainstem respiratory control system (including presumptive chemoreceptor populations), experiments in knockout mice provided no evidence for their involvement in CO2 regulation of breathing. By contrast, the alkaline-activated TASK-2 channel has a more restricted brainstem distribution and was localized to the Phox2b-expressing chemoreceptor neurons of the retrotrapezoid nucleus (RTN). Remarkably, in a Phox2b27Ala/+ mouse genetic model of congenital central hypoventilation syndrome (CCHS) that is characterized by reduced central respiratory chemosensitivity, selective ablation of Phox2b-expressing RTN neurons was accompanied by a corresponding loss of TASK-2 expression. Furthermore, genetic deletion of TASK-2 blunted RTN neuronal pH sensitivity in vitro, reduced alkaline-induced respiratory network inhibition in situ and diminished the ventilatory response to CO2/H+ in vivo. Notably, a subpopulation of RTN neurons from TASK-2−/− mice retained their pH sensitivity, at least in part due to a residual pH-sensitive background K+ current, suggesting that other mechanisms (and perhaps other K2P channels) for RTN neuronal pH sensitivity are yet to be identified.
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影响因子：
3.4
作者：
Gonzalez, J. A.;Jensen, Lise T.;Burdakov, Denis
通讯作者：
Burdakov, Denis
影响因子：
11.4
作者：
Chemin, J;Girard, C;Lazdunski, M
通讯作者：
Lazdunski, M
影响因子：
11.4
作者：
Fink, M;Duprat, F;Lazdunski, M
通讯作者：
Lazdunski, M
影响因子：
2.5
作者：
Iceman, Kimberly E.;Richerson, George B.;Harris, Michael B.
通讯作者：
Harris, Michael B.
DOI：
10.1016/s0034-5687(01)00288-2
发表时间：
2001-12-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Bayliss, DA;Talley, EM;Lei, QB
通讯作者：
Lei, QB