Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons.

Journal article

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.

Authors: González, J; Jensen, LT; Doyle, SE; Miranda-Anaya, M; Menaker, M

• Publication status: Published
• Journal: European journal of neuroscience
• Volume: 30
• Issue: 1
• Pages: 57-64
• Publication date: 2009-07-01
• DOI: 10.1111/j.1460-9568.2009.06789.x
• EISSN: 1460-9568
• ISSN: 0953-816X
• Language: English
• Keywords: Patch-Clamp Techniques; Membrane Potentials; Potassium Channels, Tandem Pore Domain; Animals; Hydrogen-Ion Concentration; Mice; Intracellular Signaling Peptides and Proteins; Action Potentials; Mice, Knockout; Green Fluorescent Proteins; Motor Activity; Mice, Transgenic; Neuropeptides; Feeding Behavior; Glucose; Brain; Neurons; Potassium Channels; Nerve Tissue Proteins