title: Acute stress diminishes M-current contributing to elevated activity of hypothalamic-pituitary-adrenal axis.
abstract: 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.
authors.affiliation: Department of Critical Care, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, PR China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: Department of Preventive Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, PR China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Psychology, University of Houston, Houston, TX, USA.
authors.forename: Therese A
authors.initials: TA
authors.lastname: Kosten
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China. Electronic address: zzm69@163.com.
authors.forename: Zongmao
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Critical Care, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: dpli@mdanderson.org.
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Li
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology*; D051656:KCNQ Potassium Channels / Q000502:physiology*; D051659:KCNQ3 Potassium Channel / Q000378:metabolism / Q000502:physiology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000502:physiology*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D051656:KCNQ Potassium Channels; D051659:KCNQ3 Potassium Channel; D021122:Protein Subunits; D003346:Corticotropin-Releasing Hormone; D000263:Adenylate Kinase; D003345:Corticosterone
keywords: AMPK; Acute stress; Corticosterone; Paraventricular nucleus; Voltage dependent K(+) channel