Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons
| العنوان: | Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons |
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| المؤلفون: | Ming-Yuan Min, Rui-Ni Wu, Ruei-Feng Chen, Hsiu-Wen Yang, Chao-Cheng Kuo |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Baclofen, Patch-Clamp Techniques, GABA Agents, Neurophysiology, Action Potentials, lcsh:Medicine, GABAB receptor, Article, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nitriles, Butadienes, Animals, Homeostasis, Autoregulation, Enzyme Inhibitors, Extracellular Signal-Regulated MAP Kinases, lcsh:Science, Receptor, gamma-Aminobutyric Acid, Neurons, Multidisciplinary, Chemistry, Kinase, lcsh:R, Cellular neuroscience, Potassium channel, Cell biology, 030104 developmental biology, Receptors, GABA-B, nervous system, GABA-B Receptor Agonists, Locus coeruleus, Female, Locus Coeruleus, lcsh:Q, Wakefulness, 030217 neurology & neurosurgery |
| الوصف: | The norepinephrine-releasing neurons in the locus coeruleus (LC) are well known to regulate wakefulness/arousal. They display active firing during wakefulness and a decreased discharge rate during sleep. We have previously reported that LC neurons express large numbers of GABAB receptors (GABABRs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABABRs by ambient GABA, which is significantly higher during sleep than during wakefulness. In this study, we further showed using western blot analysis that the activation of GABABRs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK1) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK1/2 with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK1/2 also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABABRs in mediating ERK1-dependent autoregulation of the stability of GABABR-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons. |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::796aea55854df0c2de8a648c1c66b5c7Test https://doi.org/10.1038/s41598-020-64292-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....796aea55854df0c2de8a648c1c66b5c7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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