Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons
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 GABA B receptors (GABA B Rs...
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| Veröffentlicht in: | Scientific reports 2020-05, Vol.10 (1), p.7869-7869, Article 7869 |
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| description | 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 GABA
B
receptors (GABA
B
Rs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABA
B
Rs 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 GABA
B
Rs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK
1
) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK
1/2
with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK
1/2
also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABA
B
Rs in mediating ERK
1
-dependent autoregulation of the stability of GABA
B
R-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons. |
| doi_str_mv | 10.1038/s41598-020-64292-x |
| format | Article |
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B
receptors (GABA
B
Rs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABA
B
Rs 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 GABA
B
Rs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK
1
) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK
1/2
with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK
1/2
also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABA
B
Rs in mediating ERK
1
-dependent autoregulation of the stability of GABA
B
R-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-64292-x</identifier><identifier>PMID: 32398643</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/51 ; 631/378/87 ; 631/443/376 ; 82 ; 82/80 ; 9/74 ; Arousal ; Baclofen ; Binding sites ; Brain slice preparation ; Cell membranes ; Extracellular signal-regulated kinase ; Humanities and Social Sciences ; Kinases ; Locus coeruleus ; multidisciplinary ; Neurons ; Neurosciences ; Norepinephrine ; Physiology ; Potassium channels ; Proteins ; Roles ; Science ; Science (multidisciplinary) ; Sleep and wakefulness ; γ-Aminobutyric acid B receptors</subject><ispartof>Scientific reports, 2020-05, Vol.10 (1), p.7869-7869, Article 7869</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-45c4d688a4a5e2b064115e1c75dad3dad5ba56e763fd5d7e3aebac206df143763</citedby><cites>FETCH-LOGICAL-c451t-45c4d688a4a5e2b064115e1c75dad3dad5ba56e763fd5d7e3aebac206df143763</cites><orcidid>0000-0002-0823-9388</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217949/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217949/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27911,27912,41107,42176,51563,53778,53780</link.rule.ids></links><search><creatorcontrib>Wu, Rui-Ni</creatorcontrib><creatorcontrib>Kuo, Chao-Cheng</creatorcontrib><creatorcontrib>Min, Ming-Yuan</creatorcontrib><creatorcontrib>Chen, Ruei-Feng</creatorcontrib><creatorcontrib>Yang, Hsiu-Wen</creatorcontrib><title>Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><description>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 GABA
B
receptors (GABA
B
Rs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABA
B
Rs 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 GABA
B
Rs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK
1
) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK
1/2
with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK
1/2
also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABA
B
Rs in mediating ERK
1
-dependent autoregulation of the stability of GABA
B
R-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons.</description><subject>13</subject><subject>13/51</subject><subject>631/378/87</subject><subject>631/443/376</subject><subject>82</subject><subject>82/80</subject><subject>9/74</subject><subject>Arousal</subject><subject>Baclofen</subject><subject>Binding sites</subject><subject>Brain slice preparation</subject><subject>Cell membranes</subject><subject>Extracellular signal-regulated kinase</subject><subject>Humanities and Social Sciences</subject><subject>Kinases</subject><subject>Locus coeruleus</subject><subject>multidisciplinary</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Norepinephrine</subject><subject>Physiology</subject><subject>Potassium channels</subject><subject>Proteins</subject><subject>Roles</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sleep and wakefulness</subject><subject>γ-Aminobutyric acid B receptors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9UUluFDEUtRCIRE0uwMoSGzYmHmvYIFVKSUA0IDGIpeV2_e44qrYbuxw1Z-ASOQsnw-mKmBZY-vIf3nv6-g-hp4y-YFQ0p0ky1TaEckoqyVtO9g_QMadSES44f_hHfoROUrqm5SneStY-RkeCi7appDhG38_3UzQWxjGPJv64_eg23ozkA2xKPcGA3zhvEiT8FgZXGth43OUpxBnggsdhjS-7s-6skCzsyoh0dnI3B_aXqzAC6Ys87nOM4CfsPF4GmxPuA8Q8QsneQY7Bpyfo0dqMCU7u_wX6fHH-qX9Flu8vX_fdklip2ESksnKomsZIo4CvaCUZU8BsrQYziBJqZVQFdSXWgxpqEAZWxnJaDWsmRWkv0MtZd5dXWxhs2SqaUe-i25r4TQfj9N8T7670JtzomrO6lW0ReH4vEMPXDGnSW5fubmg8hJw0l5RLwaWSBfrsH-h1yLGc-IBitazbYucC8RllY0gpwvrXMozqO7v1bLcuduuD3XpfSGImpQL2G4i_pf_D-gnCL6_7</recordid><startdate>20200512</startdate><enddate>20200512</enddate><creator>Wu, Rui-Ni</creator><creator>Kuo, Chao-Cheng</creator><creator>Min, Ming-Yuan</creator><creator>Chen, Ruei-Feng</creator><creator>Yang, Hsiu-Wen</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0823-9388</orcidid></search><sort><creationdate>20200512</creationdate><title>Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons</title><author>Wu, Rui-Ni ; Kuo, Chao-Cheng ; Min, Ming-Yuan ; Chen, Ruei-Feng ; Yang, Hsiu-Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-45c4d688a4a5e2b064115e1c75dad3dad5ba56e763fd5d7e3aebac206df143763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13</topic><topic>13/51</topic><topic>631/378/87</topic><topic>631/443/376</topic><topic>82</topic><topic>82/80</topic><topic>9/74</topic><topic>Arousal</topic><topic>Baclofen</topic><topic>Binding sites</topic><topic>Brain slice preparation</topic><topic>Cell membranes</topic><topic>Extracellular signal-regulated kinase</topic><topic>Humanities and Social Sciences</topic><topic>Kinases</topic><topic>Locus coeruleus</topic><topic>multidisciplinary</topic><topic>Neurons</topic><topic>Neurosciences</topic><topic>Norepinephrine</topic><topic>Physiology</topic><topic>Potassium channels</topic><topic>Proteins</topic><topic>Roles</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sleep and wakefulness</topic><topic>γ-Aminobutyric acid B receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Rui-Ni</creatorcontrib><creatorcontrib>Kuo, Chao-Cheng</creatorcontrib><creatorcontrib>Min, Ming-Yuan</creatorcontrib><creatorcontrib>Chen, Ruei-Feng</creatorcontrib><creatorcontrib>Yang, Hsiu-Wen</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Rui-Ni</au><au>Kuo, Chao-Cheng</au><au>Min, Ming-Yuan</au><au>Chen, Ruei-Feng</au><au>Yang, Hsiu-Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><date>2020-05-12</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>7869</spage><epage>7869</epage><pages>7869-7869</pages><artnum>7869</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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 GABA
B
receptors (GABA
B
Rs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABA
B
Rs 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 GABA
B
Rs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK
1
) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK
1/2
with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK
1/2
also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABA
B
Rs in mediating ERK
1
-dependent autoregulation of the stability of GABA
B
R-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32398643</pmid><doi>10.1038/s41598-020-64292-x</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0823-9388</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/51 631/378/87 631/443/376 82 82/80 9/74 Arousal Baclofen Binding sites Brain slice preparation Cell membranes Extracellular signal-regulated kinase Humanities and Social Sciences Kinases Locus coeruleus multidisciplinary Neurons Neurosciences Norepinephrine Physiology Potassium channels Proteins Roles Science Science (multidisciplinary) Sleep and wakefulness γ-Aminobutyric acid B receptors |
| title | Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons |
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