Role of KCNQ potassium channels in stress-induced deficit of working memory
The prefrontal cortex (PFC) mediates higher cognition but is impaired by stress exposure when high levels of catecholamines activate calcium-cAMP-protein kinase A (PKA) signaling. The current study examined whether stress and increased cAMP-PKA signaling in rat medial PFC (mPFC) reduce pyramidal cel...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
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| Series: | Neurobiology of Stress |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289519300396 |
| _version_ | 1819084824714936320 |
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| author | Amy F.T. Arnsten Lu E. Jin Nao J. Gamo Brian Ramos Constantinos D. Paspalas Yury M. Morozov Anna Kata Nigel S. Bamford Mark F. Yeckel Leonard K. Kaczmarek Lynda El-Hassar |
| author_facet | Amy F.T. Arnsten Lu E. Jin Nao J. Gamo Brian Ramos Constantinos D. Paspalas Yury M. Morozov Anna Kata Nigel S. Bamford Mark F. Yeckel Leonard K. Kaczmarek Lynda El-Hassar |
| author_sort | Amy F.T. Arnsten |
| collection | DOAJ |
| description | The prefrontal cortex (PFC) mediates higher cognition but is impaired by stress exposure when high levels of catecholamines activate calcium-cAMP-protein kinase A (PKA) signaling. The current study examined whether stress and increased cAMP-PKA signaling in rat medial PFC (mPFC) reduce pyramidal cell firing and impair working memory by activating KCNQ potassium channels. KCNQ2 channels were found in mPFC layers II/III and V pyramidal cells, and patch-clamp recordings demonstrated KCNQ currents that were increased by forskolin or by chronic stress exposure, and which were associated with reduced neuronal firing. Low dose of KCNQ blockers infused into rat mPFC improved cognitive performance and prevented acute pharmacological stress-induced deficits. Systemic administration of low doses of KCNQ blocker also improved performance in young and aged rats, but higher doses impaired performance and occasionally induced seizures. Taken together, these data demonstrate that KCNQ channels have powerful influences on mPFC neuronal firing and cognitive function, contributing to stress-induced PFC dysfunction. Keywords: cAMP-PKA, KCNQ, Pyramidal neurons, Working memory, Stress, Prefrontal cortex |
| first_indexed | 2024-12-21T20:54:36Z |
| format | Article |
| id | doaj.art-e489f815cedc44b7b83cd24a6d9b2696 |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-12-21T20:54:36Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-e489f815cedc44b7b83cd24a6d9b26962022-12-21T18:50:38ZengElsevierNeurobiology of Stress2352-28952019-11-0111Role of KCNQ potassium channels in stress-induced deficit of working memoryAmy F.T. Arnsten0Lu E. Jin1Nao J. Gamo2Brian Ramos3Constantinos D. Paspalas4Yury M. Morozov5Anna Kata6Nigel S. Bamford7Mark F. Yeckel8Leonard K. Kaczmarek9Lynda El-Hassar10Departments of Neuroscience, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USAPediatric Neurology, Cellular and Molecular Physiology, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USAPharmacology, Yale University School of Medicine, USADepartments of Neuroscience, Yale University School of Medicine, USA; Pharmacology, Yale University School of Medicine, USA; Corresponding author. Institute of Biology Valrose (iBV), Université Nice Sophia Antipolis, UMR 7277, Nice, 06100, France.The prefrontal cortex (PFC) mediates higher cognition but is impaired by stress exposure when high levels of catecholamines activate calcium-cAMP-protein kinase A (PKA) signaling. The current study examined whether stress and increased cAMP-PKA signaling in rat medial PFC (mPFC) reduce pyramidal cell firing and impair working memory by activating KCNQ potassium channels. KCNQ2 channels were found in mPFC layers II/III and V pyramidal cells, and patch-clamp recordings demonstrated KCNQ currents that were increased by forskolin or by chronic stress exposure, and which were associated with reduced neuronal firing. Low dose of KCNQ blockers infused into rat mPFC improved cognitive performance and prevented acute pharmacological stress-induced deficits. Systemic administration of low doses of KCNQ blocker also improved performance in young and aged rats, but higher doses impaired performance and occasionally induced seizures. Taken together, these data demonstrate that KCNQ channels have powerful influences on mPFC neuronal firing and cognitive function, contributing to stress-induced PFC dysfunction. Keywords: cAMP-PKA, KCNQ, Pyramidal neurons, Working memory, Stress, Prefrontal cortexhttp://www.sciencedirect.com/science/article/pii/S2352289519300396 |
| spellingShingle | Amy F.T. Arnsten Lu E. Jin Nao J. Gamo Brian Ramos Constantinos D. Paspalas Yury M. Morozov Anna Kata Nigel S. Bamford Mark F. Yeckel Leonard K. Kaczmarek Lynda El-Hassar Role of KCNQ potassium channels in stress-induced deficit of working memory Neurobiology of Stress |
| title | Role of KCNQ potassium channels in stress-induced deficit of working memory |
| title_full | Role of KCNQ potassium channels in stress-induced deficit of working memory |
| title_fullStr | Role of KCNQ potassium channels in stress-induced deficit of working memory |
| title_full_unstemmed | Role of KCNQ potassium channels in stress-induced deficit of working memory |
| title_short | Role of KCNQ potassium channels in stress-induced deficit of working memory |
| title_sort | role of kcnq potassium channels in stress induced deficit of working memory |
| url | http://www.sciencedirect.com/science/article/pii/S2352289519300396 |
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