NO/cGMP/PKG signaling pathway induces magnesium release mediated by mitoK<sub>ATP</sub> channel opening in rat hippocampal neurons

Yamanaka, Ryu; Shindo, Yutaka; Hotta, Kohji; Suzuki, Kôji; Oka, Kotaro

doi:10.1016/j.febslet.2013.06.049

Cited by 23 publications

(23 citation statements)

References 42 publications

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“…Under physiological conditions, depolarization triggers an increase of [Mg 2+ ] i in sensory neurons 6 , while glutamate exposure induces a [Mg 2+ ] i surge in forebrain and hippocampal neurons 7,8 . More recently, it was shown that activation of a nitric oxide signaling pathway can also trigger an increase of [Mg 2+ ] i in hippocampal neurons 9 . Moreover, enhanced [Mg 2+ ] i can be expected with a reduction in the levels of ATP during periods of waking and hyperactivity 10 .…”

Section: Introductionmentioning

confidence: 99%

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

et al. 2014

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Neuronal gap junction (GJ) channels composed of connexin36 (Cx36) play an important role in neuronal synchronization and network dynamics. Here we show that Cx36-containing electrical synapses between inhibitory neurons of the thalamic reticular nucleus are bi-directionally modulated by changes in intracellular free magnesium concentration ([Mg2+]i). Chimeragenesis demonstrates that the first extracellular loop of Cx36 contains a Mg2+-sensitive domain, and site-directed mutagenesis shows that the pore-lining residue D47 is critical in determining high Mg2+-sensitivity. Single channel analysis of Mg2+-sensitive chimeras and mutants reveals that [Mg2+]i controls the strength of electrical coupling mostly via gating mechanisms. In addition, asymmetric transjunctional [Mg2+]i induces strong instantaneous rectification, providing a novel mechanism for electrical rectification in homotypic Cx36 GJs. We suggest that Mg2+-dependent synaptic plasticity of Cx36-containing electrical synapses could underlie neuronal circuit reconfiguration via changes in brain energy metabolism that affects neuronal levels of intracellular ATP and [Mg2+]i.

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Section: Introductionmentioning

confidence: 99%

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

et al. 2014

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“…Our data indicated that all animals in different treatment groups learned how to find the hidden platform after 4 days of training by memorizing the signs on surrounding walls. Based on other investigations, NO can produce cGMP through soluble guanylate cyclase, and afterward cGMP activates PKG in the neurons [9,24]. Besides, according to our behavioral and molecular ….. Aβ + KT…..…”

Section: Discussionmentioning

confidence: 64%

“…As the pathogenesis of AD has not yet been determined completely, we suggest PKG signaling pathway as the probable interfering mechanism in this disorder. Based on other investigations, NO can produce cGMP through soluble guanylate cyclase, and afterward cGMP activates PKG in the neurons [9,24]. The intracellular mechanism of PKG is not well understood yet, but the role of PKG in regulating ERK has been identified.…”

Section: Discussionmentioning

confidence: 99%

The involvement of protein kinase G inhibitor in regulation of apoptosis and autophagy markers in spatial memory deficit induced by Aβ

Shariatpanahi

Khodagholi

Ashabi

et al. 2016

Fundamemntal Clinical Pharma

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The role of nitric oxide/protein kinase G (NO/PKG) in neurodegenerative disorders is controversial in different circumstances. PKG affects neurons both by itself and as a result of increased NO concentration. In this study, we examined the influence of PKG on spatial memory by intrahippocampal administration of three different concentrations of KT5823 as a PKG inhibitor. Morris water maze (MWM) was used for evaluation of behavioral alterations. We also measured the apoptosis and autophagy markers as two probable interfering pathways with PKG signaling by Western blot method. We found that in Aβ-pretreated rats, intrahippocampus infusions of 2.5, 5, and 10 μm/side of KT5823 led to a significant reduction in escape latency and traveled distance comparing to Aβ-treatment group. Our molecular findings indicated that KT5823 could induce autophagy and attenuate apoptotic markers at distinct doses. Here, we can conclude that in addition to other parameters, apoptosis, and autophagy in part have damaging and protective roles, respectively, in PKG signaling mechanisms. As autophagy-related proteins lose their functions in neurodegenerative diseases, we can suggest that autophagy can be one of the therapeutic aims for remedy of Alzheimer's disease.

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“…Brain slice preparations of cholinergic neurons of the basal forebrain of Wistar rats demonstrate that PKG alters the function of K + leak channels [ 47 ] and although the changes in K + channel function were explored with increasing pH, the effect of an environmental stressor, such as anoxia or hyperthermia, was never applied. For both the K + leak channels and K + pumps implicated as targets of PKG modulation [ 49 , 50 ], a change in either could alter the membrane potential of the bouton to alter neuronal excitability and firing capabilities. While PKG modulation appears to have a predominant effect on neuronal function during stress as seen with the drastic differences in Ca 2+ dynamics at higher temperatures, there is still a slight change in Ca 2+ dynamics at room temperature ( Fig 2C ).…”

Section: Discussionmentioning

confidence: 99%

cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae

Krill

2016

PLoS ONE

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While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms. In this study, we characterize presynaptic calcium ([Ca2+]i) dynamics at the Drosophila larval NMJ to determine the effects of high temperature stress on synaptic transmission. We investigated the neuroprotective role of PKG modulation both genetically using RNA interference (RNAi), and pharmacologically, to determine if and how PKG affects presynaptic [Ca2+]i dynamics during hyperthermia. We found that PKG activity modulates presynaptic neuronal Ca2+ responses during acute hyperthermia, where PKG activation makes neurons more sensitive to temperature-induced failure of Ca2+ flux and PKG inhibition confers thermotolerance and maintains normal Ca2+ dynamics under the same conditions. Targeted motoneuronal knockdown of PKG using RNAi demonstrated that decreased PKG expression was sufficient to confer thermoprotection. These results demonstrate that the PKG pathway regulates presynaptic motoneuronal Ca2+ signaling to influence thermotolerance of presynaptic function during acute hyperthermia.

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NO/cGMP/PKG signaling pathway induces magnesium release mediated by mitoK_ATP channel opening in rat hippocampal neurons

Abstract: Edited by Peter Brzezinski

Cited by 23 publications

References 42 publications

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

The involvement of protein kinase G inhibitor in regulation of apoptosis and autophagy markers in spatial memory deficit induced by Aβ

cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae

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NO/cGMP/PKG signaling pathway induces magnesium release mediated by mitoKATP channel opening in rat hippocampal neurons

Abstract: Edited by Peter Brzezinski

Cited by 23 publications

References 42 publications

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

The involvement of protein kinase G inhibitor in regulation of apoptosis and autophagy markers in spatial memory deficit induced by Aβ

cGMP-Dependent Protein Kinase Inhibition Extends the Upper Temperature Limit of Stimulus-Evoked Calcium Responses in Motoneuronal Boutons of Drosophila melanogaster Larvae

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NO/cGMP/PKG signaling pathway induces magnesium release mediated by mitoK_ATP channel opening in rat hippocampal neurons