Acute Stress Diminishes M‐Current in Corticotrophin‐Releasing Hormone Neurons through AMPK Activation

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Acute stress activate hypothalamus‐pituitary‐adrenal gland axis and corticotrophin‐releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of hypothalamus. However, the molecular and cellular mechanisms underlying hyperactivity of PVN‐CRH neurons in acute stress are not clear. M‐channel is regulated by AMPK activity and plays important role in the regulation of neuron activity. We hypothesized that M‐channel function is impaired in PVN‐CRH neurons during acute stress. Whole‐cell patch‐clamp recording were performed on PVN‐CRH neurons identified by specific expression of eGFP driven by the rat crh premotor. Acute stress (2‐hr restraint) profoundly increased firing rate of PVN‐CRH neurons while decreased M‐current in these neurons. M‐channel blocker XE991 induced lesser increased in firing activity of PVN‐CRH neurons in acutely stressed rats compared with unstressed rats. Microinjection of XE991 into the PVN produced significantly lesser increases in plasma corticosterone concentration in acute stress rats than in unstressed rats. Furthermore, acute stress decreased KV7.3 subunit membrane‐fraction protein expression levels while increased phosphorylated AMPK level in the PVN tissues compared with unstressed rats. However, the Kv7.3 cytoplasma‐fraction protein level and Kv7.2 subunit expression level in the PVN tissue. Treatment with AMPK inhibitor compound C not only recovered the Kv7.3 membrance‐fraction expression level but also reinstalled the reduced M‐current and XE991‐induced excitatory effect on PVN‐CRH neruons in acute stressed rats. Finally, microinjection of compound C into the PVN reinstalled XE991‐induced increase in plasma corticosterone levels. Collectively, these results suggested that acute stress diminishes M‐current in PVN‐CRH neurons, which is related to AMPK activation.Support or Funding InformationThis study was supported by NIMH grants MH096086.