Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Acute stress diminishes M-current contributing to elevated activity of hypothalamic-pituitary-adrenal axis. 2790 68