Abstract
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.
Original language | English |
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Pages (from-to) | 57-64 |
Number of pages | 8 |
Journal | European Journal of Neuroscience |
Volume | 30 |
Issue number | 1 |
DOIs | |
Publication status | Published - 29 Jun 2009 |
Bibliographical note
Acknowledgement: This work was funded by the European Research Council (FP7 grant to D.B.),and National Institutes of Health grants NS033583 (to D.A.B.) and MH074924(to M.M.).Keywords
- Action Potentials
- Animals
- Brain
- Feeding Behavior
- Glucose
- Green Fluorescent Proteins
- Hydrogen-Ion Concentration
- In Vitro Techniques
- Intracellular Signaling Peptides and Proteins
- Membrane Potentials
- Mice
- Mice, Knockout
- Mice, Transgenic
- Motor Activity
- Nerve Tissue Proteins
- Neurons
- Neuropeptides
- Orexins
- Patch-Clamp Techniques
- Potassium Channels
- Potassium Channels, Tandem Pore Domain
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't