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Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose2

Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose2
Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose2
Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance.
intracellular signaling peptides and proteins, transgenic, inhalation, proteins, mice, reward, animals, energy metabolism, patch-clamp techniques, anesthetics, metabolism, drug effects, potassium, pharmacology, protein subunits, peptides, potassium channels, green fluorescent proteins, acid, signal transduction, glucose, neuropeptides, halothane, inbred c57bl, female, behavior, physiology, neural inhibition, research, excitatory postsynaptic potentials, inbred dba, tandem pore domain, wakefulness, genetics, research support, inhibition, gene expression, neurons, acids, protein
0896-6273
711-722
Burdakov, D.
d8b3e265-8088-433e-9702-bdc71cad7e05
Jensen, L.T.
4c37c064-8167-4690-8f41-51cbb21a599f
Alexopoulos, H.
05729a8d-ce15-41aa-9e88-ebf3a57ea427
Williams, R.H.
65d5e089-4db7-4f07-9ccd-ab1c0d13daa0
Fearon, I.M.
4ef3ec41-ec62-4e73-beb6-c8548d5cdd5e
O'Kelly, I.
e640f28a-42f0-48a6-9ce2-cb5a85d08c66
Gerasimenko, O.
ff14e7f0-51ee-4466-bf13-bb6c02f43d93
Fugger, L.
ff47502b-2750-40a4-98e0-dc6e410108b6
Verkhratsky, A.
a5491dc8-c807-439b-bab4-6c8f5de59afa
Burdakov, D.
d8b3e265-8088-433e-9702-bdc71cad7e05
Jensen, L.T.
4c37c064-8167-4690-8f41-51cbb21a599f
Alexopoulos, H.
05729a8d-ce15-41aa-9e88-ebf3a57ea427
Williams, R.H.
65d5e089-4db7-4f07-9ccd-ab1c0d13daa0
Fearon, I.M.
4ef3ec41-ec62-4e73-beb6-c8548d5cdd5e
O'Kelly, I.
e640f28a-42f0-48a6-9ce2-cb5a85d08c66
Gerasimenko, O.
ff14e7f0-51ee-4466-bf13-bb6c02f43d93
Fugger, L.
ff47502b-2750-40a4-98e0-dc6e410108b6
Verkhratsky, A.
a5491dc8-c807-439b-bab4-6c8f5de59afa

Burdakov, D., Jensen, L.T., Alexopoulos, H., Williams, R.H., Fearon, I.M., O'Kelly, I., Gerasimenko, O., Fugger, L. and Verkhratsky, A. (2006) Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose2. Neuron, 50 (5), 711-722. (doi:10.1016/j.neuron.2006.04.032).

Record type: Article

Abstract

Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance.

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More information

Published date: June 2006
Keywords: intracellular signaling peptides and proteins, transgenic, inhalation, proteins, mice, reward, animals, energy metabolism, patch-clamp techniques, anesthetics, metabolism, drug effects, potassium, pharmacology, protein subunits, peptides, potassium channels, green fluorescent proteins, acid, signal transduction, glucose, neuropeptides, halothane, inbred c57bl, female, behavior, physiology, neural inhibition, research, excitatory postsynaptic potentials, inbred dba, tandem pore domain, wakefulness, genetics, research support, inhibition, gene expression, neurons, acids, protein

Identifiers

Local EPrints ID: 59542
URI: https://eprints.soton.ac.uk/id/eprint/59542
ISSN: 0896-6273
PURE UUID: b8063854-a71e-4fc2-928e-9fc9eb82cffe

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Date deposited: 03 Sep 2008
Last modified: 13 Mar 2019 20:30

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Contributors

Author: D. Burdakov
Author: L.T. Jensen
Author: H. Alexopoulos
Author: R.H. Williams
Author: I.M. Fearon
Author: I. O'Kelly
Author: O. Gerasimenko
Author: L. Fugger
Author: A. Verkhratsky

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