Lise Torp Jensen

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • J A González, Denmark
  • Lise T Jensen
  • Susan E Doyle, Denmark
  • Manuel Miranda-Anaya, Denmark
  • Michael Menaker, Denmark
  • Lars Fugger
  • Douglas A Bayliss, Denmark
  • Denis Burdakov, Denmark
  • The Department of Clinical Immunology
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 languageEnglish
JournalEuropean Journal of Neuroscience
Pages (from-to)57-64
Number of pages7
Publication statusPublished - 2009

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