Acute stress diminishes M-current contributing to elevated activity of hypothalamic-pituitary-adrenal axis.
Acute stress diminishes M-current contributing to elevated activity of hypothalamic-pituitary-adrenal axis.
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DOI：
10.1016/j.neuropharm.2016.11.024
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发表时间：
2017-03-01
影响因子：
4.7
通讯作者：
Li DP
中科院分区：
文献类型：
--
作者：
Zhou JJ;Gao Y;Kosten TA;Zhao Z;Li DP
Acute stress stimulates corticotrophin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN), which is an essential component of hypothalamic-pituitary-adrenal (HPA) axis. However, the cellular and molecular mechanisms remain unclear. The M-channel is a voltage-dependent K+ channel involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we tested our hypothesis that acute stress suppresses expression of Kv7 channels to stimulate PVN-CRH neurons and the HPA axis. Rat PVN-CRH neurons were identified by expressing enhanced green fluorescent protein driven by Crh promoter. Acute restraint stress attenuated the excitatory effect of Kv7 blocker XE-991 on the firing activity of PVN-CRH neurons and blunted the increase in plasma corticosterone (CORT) levels induced by microinjection of XE-991 into the PVN. Furthermore, acute stress significantly decreased the M-currents in PVN-CRH neurons and reduced PVN expression of Kv7.3 subunit in the membrane. In addition, acute stress significantly increased phosphorylated AMP-activated protein kinase (AMPK) levels in the PVN tissue. Intracerebroventricular injection of the AMPK inhibitor dorsomorphin restored acute stress-induced elevation of CORT levels and reduction of membrane Kv7.3 protein level in the PVN. Dorsomorphin treatment increased the M-currents and reduced the firing activity of PVN-CRH neurons in acutely stressed rats. Collectively, these data suggest that acute stress diminishes Kv7 channels to stimulate PVN-CRH neurons and the HPA axis potentially via increased AMPK activity.
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影响因子：
3.7
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通讯作者：
Hodge JJ
影响因子：
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Bhalla, Vivek;Oyster, Nicholas M.;Hallows, Kenneth R.
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MEYERHOFF, JL
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