A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra

Andoh, Tomio; Ishiwa, Dai; Kamiya, Yoshinori; Echigo, Noriyuki; Goto, Takahisa; Yamada, Yosuke

doi:10.1016/j.brainres.2006.09.085

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…2 D ). Brain K ATP channels can link to A 1 Rs (Andoh et al, 2006), and these K + channels are expressed functionally in CA3 pyramidal neurons (Griesemer et al, 2002). …”

Section: Resultsmentioning

confidence: 99%

“…In this study the K ATP channels are assumed to be opened by the traditional signal of a decrease in [ATP] i , perhaps in a localized area inside the cell; direct measurements of ATP and cell energy molecules during maintenance on a ketogenic diet reveal a net increase. As an alternate explanation, the K ATP channels could also be coupled to A 1 Rs (Andoh et al 2006). Here we focus on key aspects of a ketone-based metabolic state – increased ATP and decreased glucose – and record from a brain region and cell type relevant to both experimental seizure models and clinical seizure disorders.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and K_ATPChannels

Kawamura¹,

Ruskin²,

Masino³

2010

J. Neurosci.

163

156

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Metabolic perturbations that decrease or limit blood glucose-such as fasting or adhering to a ketogenic diet-reduce epileptic seizures significantly. To date, the critical links between altered metabolism and decreased neuronal activity remain unknown. More generally, metabolic changes accompany numerous CNS disorders, and the purines ATP and its core molecule adenosine are poised to translate cell energy into altered neuronal activity. Here we show that nonpathological changes in metabolism induce a purinergic autoregulation of hippocampal CA3 pyramidal neuron excitability. During conditions of sufficient intracellular ATP, reducing extracellular glucose induces pannexin-1 hemichannel-mediated ATP release directly from CA3 neurons. This extracellular ATP is dephosphorylated to adenosine, activates neuronal adenosine A 1 receptors, and, unexpectedly, hyperpolarizes neuronal membrane potential via ATP-sensitive K ϩ channels. Together, these data delineate an autocrine regulation of neuronal excitability via ATP and adenosine in a seizure-prone subregion of the hippocampus and offer new mechanistic insight into the relationship between decreased glucose and increased seizure threshold. By establishing neuronal ATP release via pannexin hemichannels, and hippocampal adenosine A 1 receptors coupled to ATP-sensitive K ϩ channels, we reveal detailed information regarding the relationship between metabolism and neuronal activity and new strategies for adenosine-based therapies in the CNS.

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“…2 D ). Brain K ATP channels can link to A 1 Rs (Andoh et al, 2006), and these K + channels are expressed functionally in CA3 pyramidal neurons (Griesemer et al, 2002). …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and K_ATPChannels

Kawamura¹,

Ruskin²,

Masino³

2010

J. Neurosci.

163

156

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“…Of the adenosine receptors, particularly the A 1 receptors have been suggested to be involved in the regulation of neurotransmitter release. The adenosine receptors A 1 and A 2a have been demonstrated to function in the brain stem [45] and in its various nuclei, for example in the nucleus tractus solitarius [46,47], the dorsomedial nucleus of the solitary tract [48] and the substantia nigra [49]. Glycine release was now enhanced by the A 1 receptor agonist R-PIA, which effect was reduced by the antagonist DPCPX, indicating an A 1 receptor-mediated mechanism.…”

Section: Effects Of Adenosine Receptorsmentioning

confidence: 96%

Mechanisms of Glycine Release in Mouse Brain Stem Slices

Saransaari

Oja

2008

Neurochem Res

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In the brain stem glycine is associated with multiple sensory and visceral regulations, being involved in, for instance, cardiovascular, respiratory and auditory functions. We here studied the mechanisms of the release of preloaded [(3)H]glycine from mouse brain stem slices in a superfusion system. A depolarizing concentration of K(+) ions (50 mM) evoked glycine release, but in the absence of Ca(2+) the effect was attenuated, indicating that a part of the evoked release represents Ca(2+)-dependent exocytosis. The Ca(2+)-independent release was enhanced by omission of Na(+) and Cl(-). The stimulatory effect of extracellular glycine confirmed the involvement of transporters functioning in a reverse direction. A part of the release is mediated by Na(+) and Cl(-) channels, since it was inhibited by the inhibitors of these, riluzole and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonate, respectively. Glycine release was potentiated by the activation of protein kinase C and diminished by increasing cyclic guanosine monophosphate levels with a phosphodiesterase inhibitor, zaprinast. The release was also modulated by the phospholipase inhibitor quinacrine and the tyrosine kinase inhibitor genistein. Adenosine A(1) receptors likewise regulate glycine release, since it was enhanced by their agonist R(-)N(6)-(2-phenylisopropyl)adenosine, which effect was blocked by the antagonist 8-cyclopentyl-1,3-dipropylxanthine. The ionotropic glutamate receptor agonists N-methyl-D: -aspartate, kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate failed to have any effects contrary to their effects in higher brain regions, e.g., in the hippocampus. The group I and III metabotropic glutamate receptor agonists (S)-3,5-dihydroxyphenylglycine and O-phospho-L: -serine, respectively, increased the release in a receptor-mediated manner. Glycine release in the brain stem was also markedly enhanced by cell-damaging conditions, including hypoxia, hypoglycemia and ischemia.

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“…This utilization of ketones, which are a less efficient substrate for glycolysis, promotes mitochondrial adaptation via increased transcription of mitochondrial genes, thereby enhancing mitochondrial biogenesis and bioenergetic efficiency [121]. This increased mitochondrial efficiency promotes rapid turnover of ATP to adenosine, thereby promoting enhanced signaling via P1- A1 receptors and subsequent suppression of seizures [122]. Taken together, these data demonstrate that intimate purinergic interactions between astrocytes and neurons are instrumental for neuronal integrity.…”

Section: Purinergic Signalingmentioning

confidence: 99%

Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

Lindberg¹,

Shan²,

Ayers-Ringler³

et al. 2015

CMM

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Purinergic signaling regulates numerous vital biological processes in the central nervous system (CNS). The two principle purines, ATP and adenosine act as excitatory and inhibitory neurotransmitters, respectively. Compared to other classical neurotransmitters, the role of purinergic signaling in psychiatric disorders is not well understood or appreciated. Because ATP exerts its main effect on energy homeostasis, neuronal function of ATP has been underestimated. Similarly, adenosine is primarily appreciated as a precursor of nucleotide synthesis during active cell growth and division. However, recent findings suggest that purinergic signaling may explain how neuronal activity is associated neuronal energy charge and energy homeostasis, especially in mental disorders. In this review, we provide an overview of the synaptic function of mitochondria and purines in neuromodulation, synaptic plasticity, and neuron-glia interactions. We summarize how mitochondrial and purinergic dysfunction contribute to mental illnesses such as schizophrenia, bipolar disorder, autism spectrum disorder (ASD), depression, and addiction. Finally, we discuss future implications regarding the pharmacological targeting of mitochondrial and purinergic function for the treatment of psychiatric disorders.

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A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra

Cited by 19 publications

References 29 publications

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and K_ATPChannels

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and K_ATPChannels

Mechanisms of Glycine Release in Mouse Brain Stem Slices

Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

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A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra

Cited by 19 publications

References 29 publications

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and KATPChannels

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and KATPChannels

Mechanisms of Glycine Release in Mouse Brain Stem Slices

Purinergic Signaling and Energy Homeostasis in Psychiatric Disorders

Contact Info

Product

Resources

About

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and K_ATPChannels

Metabolic Autocrine Regulation of Neurons Involves Cooperation among Pannexin Hemichannels, Adenosine Receptors, and K_ATPChannels