Dual Orexin Actions on Dorsal Raphe and Laterodorsal Tegmentum Neurons: Noisy Cation Current Activation and Selective Enhancement of Ca<sup>2+</sup> Transients Mediated by L-Type Calcium Channels

Kohlmeier, Kristi A.; Watanabe, S.; Tyler, Christopher J.; Burlet, Sophie; Leonard, Christopher

doi:10.1152/jn.01388.2007

Cited by 77 publications

(101 citation statements)

References 81 publications

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“…Previous reports have suggested that VGCCs provide an important pathway for orexin-A-induced calcium signal (Uramura et al, 2001;Xu et al, 2002;Kohlmeier et al, 2008). Therefore, the effect of orexin-A on VGCCs was investigated in cultured rat hypothalamic NPY neurons, which are involved in the orexigenic effect of orexin-A.…”

Section: Resultsmentioning

confidence: 99%

“…AMPK can be indirectly activated by cytosolic free Ca 21 ([Ca 21 ] i ) via Ca 21 -sensitive calmodulin-dependent protein kinase kinases (CaMKKs) (Anderson et al, 2008;Bair et al, 2009;Fogarty et al, 2010). It has been demonstrated that appetite-regulating hormones such as ghrelin and orexin-A increase [Ca 21 ] i in many native neurons, including NPY neurons (Uramura et al, 2001;Xu et al, 2002;Kohlmeier et al, 2008). Thus, calcium-dependent activation of AMPK may couple orexin-A's action with the NPYergic system.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, calcium-dependent activation of AMPK may couple orexin-A's action with the NPYergic system. Voltage-gated calcium channels (VGCCs) are the main route of calcium entry in neurons (Uramura et al, 2001;Xu et al, 2002;Kohlmeier et al, 2008). However, there are few reports about the role of VGCCs in AMPK activation.…”

Section: Introductionmentioning

confidence: 99%

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Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Zhou

et al. 2013

Mol Pharmacol

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Hypothalamic AMP-activated protein kinase (AMPK) and orexins/ hypocretins are both involved in the control of feeding behavior, but little is known about the interaction between these two signaling systems. Here, we demonstrated that orexin-A elicited significant activation of AMPK in the arcuate nucleus (ARC) of the hypothalamus by elevating cytosolic free Ca 21 involving extracellular calcium influx. Electrophysiological results revealed that orexin-A increased the L-type calcium current via the orexin receptor-phospholipase C-protein kinase C signaling pathway in ARC neurons that produce neuropeptide Y, an important downstream effector of orexin-A's orexigenic effect. Furthermore, the L-type calcium channel inhibitor nifedipine attenuated orexin-A-induced AMPK activation in vitro and in vivo. We found that inhibition of AMPK by either compound C (6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)-pyrazolo[1,5-a]pyrimidine) or the ATPmimetic 9-b-D-arabinofuranoside prevented the appetite-stimulating effect of orexin-A. This action can be mimicked by nifedipine, the blocker of the L-type calcium channel. Our results indicated that orexin-A activates hypothalamic AMPK signaling through a Ca 21 -dependent mechanism involving the voltage-gated L-type calcium channel, which may serve as a potential target for regulating feeding behavior.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Zhou

et al. 2013

Mol Pharmacol

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“…Adenosine deaminase is a marker of histaminergic neurons (Senba et al, 1985). These antibodies have been used in previous studies and labeled neurons in a manner consistent with well known gene/protein expression patterns (Senba et al, 1985;Abumaria et al, 2007;Adamantidis et al, 2007;Kohlmeier et al, 2008). At 16 h later, the sections were processed according to the same protocol above, but instead of using DAB with nickel solution for the final staining step, we used DAB alone (Vector Laboratories) to create a brown staining product.…”

Section: Methodsmentioning

confidence: 99%

Sleep Homeostasis Modulates Hypocretin-Mediated Sleep-to-Wake Transitions

Carter¹,

Adamantidis²,

Ohtsu³

et al. 2009

J. Neurosci.

223

160

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The hypocretins (Hcrts) (also called orexins) are two neuropeptides expressed in the lateral hypothalamus that play a crucial role in the stability of wakefulness. Previously, our laboratory demonstrated that in vivo photostimulation of Hcrt neurons genetically targeted with ChR2, a light-activated cation channel, was sufficient to increase the probability of an awakening event during both slow-wave sleep and rapid eye movement sleep. In the current study, we ask whether Hcrt-mediated sleep-to-wake transitions are affected by light/dark period and sleep pressure. We found that stimulation of Hcrt neurons increased the probability of an awakening event throughout the entire light/dark period but that this effect was diminished with sleep pressure induced by 2 or 4 h of sleep deprivation. Interestingly, photostimulation of Hcrt neurons was still sufficient to increase activity assessed by c-Fos expression in Hcrt neurons after sleep deprivation, although this stimulation did not cause an increase in transitions to wakefulness. In addition, we found that photostimulation of Hcrt neurons increases neural activity assessed by c-Fos expression in the downstream arousal-promoting locus ceruleus and tuberomammilary nucleus but not after 2 h of sleep deprivation. Finally, stimulation of Hcrt neurons was still sufficient to increase the probability of an awakening event in histidine decarboxylase-deficient knock-out animals. Collectively, these results suggest that the Hcrt system promotes wakefulness throughout the light/dark period by activating multiple downstream targets, which themselves are inhibited with increased sleep pressure.

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“…Whereas OXA signals through both OX1R and OX2R, OXB is thought to operate mainly through OX2R (Scammell and Winrow, 2011;Gotter et al, 2012). The effects of OX peptides on their cognate receptors are mediated intracellularly through a rise in cytosolic calcium (Ca 21 cyt ) occurring primarily through intracellular calcium release channels, even if other mechanisms implicating voltage-dependent calcium channels (VDCCs) and transient receptor potential channels have also been described (Kukkonen et al, 2001;Kohlmeier et al, 2008;Nakamura et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The Sleep-Modulating Peptide Orexin-B Protects Midbrain Dopamine Neurons from Degeneration, Alone or in Cooperation with Nicotine

et al. 2014

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To determine whether orexinergic hypothalamic peptides can influence the survival of brainstem dopamine (DA) neurons, we used a model system of rat midbrain cultures in which DA neurons degenerate spontaneously and progressively as they mature. We established that orexin (OX)-B provides partial but significant protection to spontaneously dying DA neurons, whereas the homologous peptide OXA has only marginal effects. Importantly, DA neurons rescued by OXB accumulated DA efficiently by active transport, suggesting that they were functional. G-proteincoupled OX1 and OX2 receptors were both present on DA neurons, but the protective effect of OXB was attributable solely to OX2 receptors; a selective inhibitor of this receptor subtype,amino]-N-(3-pyridinylmethyl)-acetamide (EMPA), suppressed this effect, whereas a selective agonist, [Ala 11 , ]OXB, reproduced it. Survival promotion by OXB required intracellular calcium mobilization via inositol-1,4,5-triphosphate and ryanodine receptors. Nicotine, a well known neuroprotective molecule for DA neurons, improved OXB-mediated rescue through the activation of a-bungarotoxin-sensitive (presumably a7) nicotinic receptors, although nicotine had no effect on its own. Altogether, our data suggest that the loss of hypothalamic orexinergic neurons that occurs in Parkinson's disease might confer an increased vulnerability to midbrain DA neurons in this disorder.

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Dual Orexin Actions on Dorsal Raphe and Laterodorsal Tegmentum Neurons: Noisy Cation Current Activation and Selective Enhancement of Ca²⁺ Transients Mediated by L-Type Calcium Channels

Abstract: Kohlmeier KA, Watanabe S, Tyler CJ, Burlet S, Leonard CS. Dual orexin actions on dorsal raphe and laterodorsal tegmentum neurons: noisy cation current activation and selective enhancement of Ca 2ϩ transients mediated by L-type calcium channels.

Cited by 77 publications

References 81 publications

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Sleep Homeostasis Modulates Hypocretin-Mediated Sleep-to-Wake Transitions

The Sleep-Modulating Peptide Orexin-B Protects Midbrain Dopamine Neurons from Degeneration, Alone or in Cooperation with Nicotine

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Dual Orexin Actions on Dorsal Raphe and Laterodorsal Tegmentum Neurons: Noisy Cation Current Activation and Selective Enhancement of Ca2+ Transients Mediated by L-Type Calcium Channels

Abstract: Kohlmeier KA, Watanabe S, Tyler CJ, Burlet S, Leonard CS. Dual orexin actions on dorsal raphe and laterodorsal tegmentum neurons: noisy cation current activation and selective enhancement of Ca 2ϩ transients mediated by L-type calcium channels.

Cited by 77 publications

References 81 publications

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca2+-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca2+-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Sleep Homeostasis Modulates Hypocretin-Mediated Sleep-to-Wake Transitions

The Sleep-Modulating Peptide Orexin-B Protects Midbrain Dopamine Neurons from Degeneration, Alone or in Cooperation with Nicotine

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Dual Orexin Actions on Dorsal Raphe and Laterodorsal Tegmentum Neurons: Noisy Cation Current Activation and Selective Enhancement of Ca²⁺ Transients Mediated by L-Type Calcium Channels

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel

Orexin-A Activates Hypothalamic AMP-Activated Protein Kinase Signaling through a Ca²⁺-Dependent Mechanism Involving Voltage-Gated L-Type Calcium Channel