Pre‐synaptic kainate receptor‐mediated facilitation of glutamate release involves <scp>PKA</scp> and Ca<sup>2+</sup>‐calmodulin at thalamocortical synapses

Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Sihra, Talvinder S.; Rodríguez‐Moreno, Antonio

doi:10.1111/jnc.12310

Cited by 31 publications

(41 citation statements)

References 46 publications

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“…Importantly, in neuronal cells, Ca 2+ entry via the G-protein coupled mechanism has also been implicated in the shaping of action potentials, synaptic transmission and sensory transduction [23,24]. Additionally, changes in [Ca 2+ ] i are also known to regulate the motility of many cellular structures, including the axonal growth cones [25] and the dendritic filopodia of developing neurons [26].…”

Section: Trpc Channels Properties and Their Mode Of Activationmentioning

confidence: 99%

Physiological Function and Characterization of TRPCs in Neurons

Sun

Sukumaran

Bandyopadhyay

et al. 2014

Cells

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Ca2+ entry is essential for regulating vital physiological functions in all neuronal cells. Although neurons are engaged in multiple modes of Ca2+ entry that regulates variety of neuronal functions, we will only discuss a subset of specialized Ca2+-permeable non-selective Transient Receptor Potential Canonical (TRPC) channels and summarize their physiological and pathological role in these excitable cells. Depletion of endoplasmic reticulum (ER) Ca2+ stores, due to G-protein coupled receptor activation, has been shown to activate TRPC channels in both excitable and non-excitable cells. While all seven members of TRPC channels are predominately expressed in neuronal cells, the ion channel properties, mode of activation, and their physiological responses are quite distinct. Moreover, many of these TRPC channels have also been suggested to be associated with neuronal development, proliferation and differentiation. In addition, TRPCs also regulate neurosecretion, long-term potentiation and synaptic plasticity. Similarly, perturbations in Ca2+ entry via the TRPC channels have been also suggested in a spectrum of neuropathological conditions. Hence, understanding the precise involvement of TRPCs in neuronal function and in neurodegenerative conditions would presumably unveil avenues for plausible therapeutic interventions for these devastating neuronal diseases.

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Section: Trpc Channels Properties and Their Mode Of Activationmentioning

confidence: 99%

Physiological Function and Characterization of TRPCs in Neurons

Sun

Sukumaran

Bandyopadhyay

et al. 2014

Cells

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“…Intriguingly, however, KARs have also been shown to facilitate glutamate release upon application of nanomolar concentrations of kainate. This facilitation of glutamate release requires KAR activation resulting in the accumulation of presynaptic calcium, the production of Ca 2+ -calmodulin complexes and the activation adenylate cyclase and PKA [113][114][115]. Thus, at certain synapses, KARs can exert bidirectional modulatory actions on glutamate release related to the extent of their activation (for recent review see [3]).…”

Section: Kar Regulation Of Excitatory Neurotransmissionmentioning

confidence: 99%

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

et al. 2017

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Kainate receptors (KARs) are glutamate-gated ion channels that play fundamental roles in regulating neuronal excitability and network function in the brain. After being cloned in the 1990s, important progress has been made in understanding the mechanisms controlling the molecular and cellular properties of KARs, and the nature and extent of their regulation of wider neuronal activity. However, there have been significant recent advances towards understanding KAR trafficking through the secretory pathway, their precise synaptic positioning, and their roles in synaptic plasticity and disease. Here we provide an overview highlighting these new findings about the mechanisms controlling KARs and how KARs, in turn, regulate other proteins and pathways to influence synaptic function.

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“…In synaptic terminals, an increase in cytosolic Ca 2+ has been shown to activate the Ca 2+ ‐calmodulin/adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) cascade, thereby facilitating glutamate release (Andrade‐Talavera, Duque‐Feria, Sihra, & Rodríguez‐Moreno, ; Rodríguez‐Moreno & Sihra, ). Therefore, we hypothesize that the allopregnanolone‐mediated inhibition of glutamate release is related to the decrease in Ca 2+ activating calmodulin cascade.…”

Section: Resultsmentioning

confidence: 99%

“…An increase in cytosolic Ca 2+ in the nerve terminals is known to affect a Ca 2+ /calmodulin‐dependent activation of AC, including AC1 and AC8 (Cooper, ; Wang & Storm, ). The activation of these ACs increases cAMP levels and activates PKA, which enhances glutamate release (Andrade‐Talavera et al, ; Rodríguez‐Moreno & Sihra, ). Whether the observed inhibitory effect of allopregnanolone on the intrasynaptosomal Ca 2+ levels causes a suppression of the Ca 2+ ‐calmodulin/AC/cAMP/PKA cascade, thereby reducing glutamate release.…”

Section: Discussionmentioning

confidence: 99%

Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals

Chang

Hsieh

Huang

et al. 2018

Synapse

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Allopregnanolone, an active metabolite of progesterone, has been reported to exhibit neuroprotective activity in several preclinical models. Considering that the excitotoxicity caused by excessive glutamate is implicated in many brain disorders, the effect of allopregnanolone on glutamate release in rat cerebrocortical nerve terminals and possible underlying mechanism were investigated. We observed that allopregnanolone inhibited 4‐aminopyridine (4‐AP)‐evoked glutamate release, and this inhibition was prevented by chelating the extracellular Ca2+ ions and the vesicular transporter inhibitor. Allopregnanolone reduced the elevation of 4‐AP‐evoked intrasynaptosomal Ca2+ levels, but did not affect the synaptosomal membrane potential. In the presence of N‐, P/Q‐, and R‐type channel blockers, allopregnanolone‐mediated inhibition of 4‐AP‐evoked glutamate release was markedly reduced; however, the intracellular Ca2+‐release inhibitors did not affect the allopregnanolone effect. Furthermore, allopregnanolone‐mediated inhibition of 4‐AP‐evoked glutamate release was completely abolished in the synaptosomes pretreated with inhibitors of Ca2+/calmodulin, adenylate cyclase, and protein kinase A (PKA), namely calmidazolium, MDL12330A, and H89, respectively. Additionally, the allopregnanolone effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Our data are the first to suggest that allopregnanolone reduce the Ca2+ influx through N‐, P/Q‐, and R‐type Ca2+ channels, through the activation of GABAA receptors present on cerebrocortical nerve terminals, subsequently suppressing the Ca2+‐calmodulin/PKA cascade and decreasing 4‐AP‐evoked glutamate release.

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Pre‐synaptic kainate receptor‐mediated facilitation of glutamate release involves PKA and Ca²⁺‐calmodulin at thalamocortical synapses

Cited by 31 publications

References 46 publications

Physiological Function and Characterization of TRPCs in Neurons

Physiological Function and Characterization of TRPCs in Neurons

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals

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Pre‐synaptic kainate receptor‐mediated facilitation of glutamate release involves PKA and Ca2+‐calmodulin at thalamocortical synapses

Cited by 31 publications

References 46 publications

Physiological Function and Characterization of TRPCs in Neurons

Physiological Function and Characterization of TRPCs in Neurons

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals

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Pre‐synaptic kainate receptor‐mediated facilitation of glutamate release involves PKA and Ca²⁺‐calmodulin at thalamocortical synapses