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- W4280493331 abstract "Abstract Glutamate N‐methyl‐ d ‐aspartate (NMDA) receptors (NMDARs) and Kv7/M channels are importantly involved in regulating neuronal activity involved in various physiological and pathological functions. Corticotropin‐releasing hormone (CRH)‐expressing neurons in the central nucleus of the amygdala (CeA) critically mediate autonomic response during stress. However, the interaction between NMDA receptors and Kv7/M channels in the CRH CeA neurons remains unclear. In this study, we identified rat CRH CeA neurons through the expression of an AAV viral vector‐mediated enhanced green fluorescent protein (eGFP) driven by the rat CRH promoter. M‐currents carried by Kv7/M channels were recorded using the whole‐cell patch‐clamp approach in eGFP‐tagged CRH CeA neurons in brain slices. Acute exposure to NMDA significantly reduced M‐currents recorded from the CRH CeA neurons. NMDA‐induced suppression of M‐currents was eliminated by chelating intracellular Ca 2+ , supplying phosphatidylinositol 4,5‐bisphosphate (PIP2) intracellularly, or blocking phosphoinositide3‐kinase (PI3K). In contrast, inhibiting protein kinase C (PKC) or calmodulin did not alter NMDA‐induced suppression of M‐currents. Sustained exposure of NMDA decreased Kv7.3 membrane protein levels and suppressed M‐currents, while the Kv7.2 expression levels remained unaltered. Pre‐treatment of brain slices with PKC inhibitors alleviated the decreases in Kv7.3 and reduction of M‐currents in CRH CeA neurons induced by NMDA. PKC inhibitors did not alter Kv7.2 and Kv7.3 membrane protein levels and M‐currents in CRH CeA neurons. These data suggest that transient activation of NMDARs suppresses M‐currents through the Ca 2+ ‐dependent PI3K‐PIP2 signaling pathway. In contrast, sustained activation of NMDARs reduces Kv7.3 protein expression and suppresses M‐currents through a PKC‐dependent pathway. image" @default.
- W4280493331 created "2022-05-22" @default.
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- W4280493331 date "2022-05-30" @default.
- W4280493331 modified "2023-10-15" @default.
- W4280493331 title "Signaling pathways involved in <scp>NMDA</scp>‐induced suppression of M‐channels in corticotropin‐releasing hormone neurons in central amygdala" @default.
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- W4280493331 doi "https://doi.org/10.1111/jnc.15647" @default.
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