Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons.
The firing of hypothalamic hypocretin/orexin neurons is vital for normal sleep-wake transitions, but its molecular determinants are not well understood. It was recently proposed that TASK (TWIK-related acid-sensitive potassium) channels [TASK1 (K(2P)3.1) and/or TASK3 (K(2P)9.1)] regulate neuronal fi...
| Główni autorzy: | , , , , , , , |
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| Format: | Journal article |
| Język: | English |
| Wydane: |
2009
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| _version_ | 1826256527772614656 |
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| author | González, J Jensen, LT Doyle, SE Miranda-Anaya, M Menaker, M Fugger, L Bayliss, D Burdakov, D |
| author_facet | González, J Jensen, LT Doyle, SE Miranda-Anaya, M Menaker, M Fugger, L Bayliss, D Burdakov, D |
| author_sort | González, J |
| collection | OXFORD |
| description | The firing of hypothalamic hypocretin/orexin neurons is vital for normal sleep-wake transitions, but its molecular determinants are not well understood. It was recently proposed that TASK (TWIK-related acid-sensitive potassium) channels [TASK1 (K(2P)3.1) and/or TASK3 (K(2P)9.1)] regulate neuronal firing and may contribute to the specialized responses of orexin neurons to glucose and pH. Here we tested these theories by performing patch-clamp recordings from orexin neurons directly identified by targeted green fluorescent protein labelling in brain slices from TASK1/3 double-knockout mice. The deletion of TASK1/3 channels significantly reduced the ability of orexin cells to generate high-frequency firing. Consistent with reduced excitability, individual action potentials from knockout cells had lower rates of rise, higher thresholds and more depolarized after-hyperpolarizations. However, orexin neurons from TASK1/3 knockout mice retained typical responses to glucose and pH, and the knockout animals showed normal food-anticipatory locomotor activity. Our results support a novel role for TASK genes in enhancing neuronal excitability and promoting high-frequency firing, but suggest that TASK1/3 subunits are not essential for orexin cell responses to glucose and pH. |
| first_indexed | 2024-03-06T18:03:38Z |
| format | Journal article |
| id | oxford-uuid:00ab98ee-cfeb-455e-a68c-6ef17a1a4229 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:03:38Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:00ab98ee-cfeb-455e-a68c-6ef17a1a42292022-03-26T08:30:49ZDeletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:00ab98ee-cfeb-455e-a68c-6ef17a1a4229EnglishSymplectic Elements at Oxford2009González, JJensen, LTDoyle, SEMiranda-Anaya, MMenaker, MFugger, LBayliss, DBurdakov, DThe firing of hypothalamic hypocretin/orexin neurons is vital for normal sleep-wake transitions, but its molecular determinants are not well understood. It was recently proposed that TASK (TWIK-related acid-sensitive potassium) channels [TASK1 (K(2P)3.1) and/or TASK3 (K(2P)9.1)] regulate neuronal firing and may contribute to the specialized responses of orexin neurons to glucose and pH. Here we tested these theories by performing patch-clamp recordings from orexin neurons directly identified by targeted green fluorescent protein labelling in brain slices from TASK1/3 double-knockout mice. The deletion of TASK1/3 channels significantly reduced the ability of orexin cells to generate high-frequency firing. Consistent with reduced excitability, individual action potentials from knockout cells had lower rates of rise, higher thresholds and more depolarized after-hyperpolarizations. However, orexin neurons from TASK1/3 knockout mice retained typical responses to glucose and pH, and the knockout animals showed normal food-anticipatory locomotor activity. Our results support a novel role for TASK genes in enhancing neuronal excitability and promoting high-frequency firing, but suggest that TASK1/3 subunits are not essential for orexin cell responses to glucose and pH. |
| spellingShingle | González, J Jensen, LT Doyle, SE Miranda-Anaya, M Menaker, M Fugger, L Bayliss, D Burdakov, D Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. |
| title | Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. |
| title_full | Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. |
| title_fullStr | Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. |
| title_full_unstemmed | Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. |
| title_short | Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. |
| title_sort | deletion of task1 and task3 channels disrupts intrinsic excitability but does not abolish glucose or ph responses of orexin hypocretin neurons |
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