Linked Life Data

19508695

Source:http://linkedlifedata.com/resource/pubmed/id/19508695

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-7-7
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1460-9568
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-64
pubmed:dateRevised
2011-6-6
pubmed:meshHeading
pubmed-meshheading:19508695-Action Potentials, pubmed-meshheading:19508695-Animals, pubmed-meshheading:19508695-Brain, pubmed-meshheading:19508695-Feeding Behavior, pubmed-meshheading:19508695-Glucose, pubmed-meshheading:19508695-Green Fluorescent Proteins, pubmed-meshheading:19508695-Hydrogen-Ion Concentration, pubmed-meshheading:19508695-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:19508695-Membrane Potentials, pubmed-meshheading:19508695-Mice, pubmed-meshheading:19508695-Mice, Knockout, pubmed-meshheading:19508695-Mice, Transgenic, pubmed-meshheading:19508695-Motor Activity, pubmed-meshheading:19508695-Nerve Tissue Proteins, pubmed-meshheading:19508695-Neurons, pubmed-meshheading:19508695-Neuropeptides, pubmed-meshheading:19508695-Patch-Clamp Techniques, pubmed-meshheading:19508695-Potassium Channels, pubmed-meshheading:19508695-Potassium Channels, Tandem Pore Domain
pubmed:year
2009
pubmed:articleTitle
Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons.
pubmed:affiliation
Department of Pharmacology, University of Cambridge, Cambridge CB2 1 PD, UK.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural