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学科主题: 临床医学
题名:
Blockade of Na+/H+ exchanger type 3 causes intracellular acidification and hyperexcitability via inhibition of pH-sensitive K+ channels in chemosensitive respiratory neurons of the dorsal vagal nucleus in rats
作者: Zhang, Jing1; Peng, Hui2,3; Veasey, Sigrid C.4,5; Ma, Jing1; Wang, Guang-Fa1; Wang, Ke-Wei2,3
关键词: Na+/H+ exchange ; potassium channel ; dorsal vagal nucleus ; in situ hybridization ; respiration
刊名: NEUROSCIENCE BULLETIN
发表日期: 2014-02-01
DOI: 10.1007/s12264-013-1373-4
卷: 30, 期:1, 页:43-52
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: OBSTRUCTIVE SLEEP-APNEA ; BRAIN-STEM SLICES ; POTASSIUM CHANNELS ; IN-VITRO ; MEDULLARY NEURONS ; EXTRACELLULAR PH ; TASK-1 ; CHEMORECEPTION ; ACTIVATION ; CONTRIBUTE
英文摘要:

Extracellular pH (pH(e)) and intracellular pH (pH(i)) are important factors for the excitability of chemosensitive central respiratory neurons that play an important role in respiration and obstructive sleep apnea. It has been proposed that inhibition of central Na+/ H+ exchanger 3 (NHE-3), a key pHi regulator in the brainstem, decreases the pH(i), leading to membrane depolarization for the maintenance of respiration. However, how intracellular pH affects the neuronal excitability of respiratory neurons remains largely unknown. In this study, we showed that NHE-3 mRNA is widely distributed in respiration-related neurons of the rat brainstem, including the dorsal vagal nucleus (DVN). Whole-cell patch clamp recordings from DVN neurons in brain slices revealed that the standing outward current (I (so)) through pH-sensitive K+ channels was inhibited in the presence of the specific NHE-3 inhibitor AVE0657 that decreased the pHi. Exposure of DVN neurons to an acidified pH(e) and AVE0657 (5 mu mol/L) resulted in a stronger effect on firing rate and I (so) than acidified pH(e) alone. Taken together, our results showed that intracellular acidification by blocking NHE-3 results in inhibition of a pHsensitive K+ current, leading to synergistic excitation of chemosensitive DVN neurons for the regulation of respiration.

语种: 英语
所属项目编号: 30900646 ; 81241004
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000330980500004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58395
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Resp & Crit Care Med, Beijing 100034, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Beijing 100034, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Mol & Cellular Pharmacol, Beijing 100034, Peoples R China
4.Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA
5.Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

Recommended Citation:
Zhang, Jing,Peng, Hui,Veasey, Sigrid C.,et al. Blockade of Na+/H+ exchanger type 3 causes intracellular acidification and hyperexcitability via inhibition of pH-sensitive K+ channels in chemosensitive respiratory neurons of the dorsal vagal nucleus in rats[J]. NEUROSCIENCE BULLETIN,2014,30(1):43-52.
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