Characterization of a Barium‐sensitive Outward Current following Glutamate Application on Rat Midbrain Dopaminergic Cells

Mercuri, Nicola Biagio; Bonci, Antonello; Calabresi, Paolo; Bernardi, Giorgio

doi:10.1111/j.1460-9568.1996.tb01321.x

Cited by 8 publications

(8 citation statements)

References 44 publications

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“…All recorded neurons were located rostrally, with respect to the medial terminal nucleus of the accessory optic tract. DA neurons were identified both visually and on the basis of their electrophysiological properties, by the presence of a prominent time-dependent I h , in response to hyperpolarizing voltage steps (Mercuri et al, 1996). sEPSCs and sIPSCs were filtered at 1 kHz, digitized at 10 kHz, and recorded on computer using the pClamp9 software (Axon Instruments).…”

Section: Slice Preparation and Patch-clamp Techniquementioning

confidence: 99%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

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148

117

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In the present study, we used electrophysiological, biochemical, and confocal microscopy techniques, to investigate the functional role of transient receptor potential vanilloid type 1 (TRPV1) and cannabinoid type 1 receptors (CB1-R) in the substantia nigra pars compacta (SNpc) and their stimulation by the endocannabinoid N-arachidonoyl-dopamine (NADA). Liquid chromatography-mass spectrometry analyses revealed that a NADA-like compound is produced in substantia nigra slices, in conditions of hyperactivity. Moreover, the functional role of both TRPV1 and CB1-R in modulating synaptic transmission in this area was suggested by confocal microscopy data, showing TRPV1 and CB1-R immunoreactivity in punctate structures, probably representing synaptic contacts on cell bodies of the SNpc. In patch-clamp recordings from dopamine (DA) neurons of the SNpc, we found that NADA increases or reduces glutamatergic transmission onto DA neurons by activating TRPV1 and CB1 receptors, respectively, whereas it decreases GABAergic transmission via CB1 stimulation. Facilitation of glutamate release through TRPV1 was blocked in the presence of a selective blocker of the putative endocannabinoid membrane transporter (EMT), indicating that NADA needs to be taken up by cells to interact with this receptor. In line with these data, biochemical results demonstrated that NADA selectively acted at CB1-R when its re-uptake was blocked. Altogether these data demonstrate a significant role exerted by the endocannabinoid/endovanilloid NADA in the regulation of synaptic transmission to DA neurons of the SNpc. Moreover, they highlight a key function of the EMT transporter in promoting the stimulation of TRPV1 or CB1-R, thus favoring facilitation or inhibition of glutamate synaptic release.

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Section: Slice Preparation and Patch-clamp Techniquementioning

confidence: 99%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

Self Cite

148

117

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“…Most of the recorded neurons were located rostrally with respect to the medial terminal nucleus of the accessory optic tract. Dopaminergic neurons were identified on the basis of their electrophysiological properties (i.e., by the presence of a prominent time-dependent I h ) in response to hyperpolarizing voltage steps (Mercuri et al, 1996).…”

Section: Electrophysiological Characteristics Of the Dopaminergic Neumentioning

confidence: 99%

Presynaptic Facilitation of Glutamatergic Synapses to Dopaminergic Neurons of the Rat Substantia Nigra by Endogenous Stimulation of Vanilloid Receptors

et al. 2003

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Growing evidence regarding the function of vanilloid receptor-1 (VR1) in the brain suggests potential central roles of this receptor, previously described to occur primarily in peripheral sensory neurons. In the present study, we used electrophysiological and biochemical techniques to investigate the function and the endogenous stimulation of VR1 in dopaminergic neurons of the substantia nigra pars compacta (SNc). The VR1 agonist capsaicin increased the frequency of both TTX-sensitive and -insensitive spontaneous EPSCs (sEPSCs) without affecting their amplitude, suggesting a presynaptic site of action. In contrast, no effect was detected with regard to GABAergic transmission. No increase in sEPSC frequency was observed in the presence of cadmium chloride, while the voltage-dependent calcium channel antagonist omega-conotoxin MVIIC did not prevent capsaicin action. The VR1 antagonists capsazepine and iodoresiniferatoxin (IRTX) blocked the effects of capsaicin. Importantly, IRTX per se reduced sEPSC frequency, suggesting a tonic activity of VR1. The endogenous VR1 agonist anandamide (AEA) produced an IRTX-sensitive increase in the frequency of sEPSCs on dopaminergic neurons that was more pronounced when protein kinase A had been activated. Furthermore, mass spectrometric analyses and binding experiments revealed high levels of endogenous AEA and specific binding of AEA to VR1 receptors in the SNc. These data suggest a tonic facilitation of glutamate release exerted by VR1 in the SNc through a stimulation of VR1 by endovanilloids, including anandamide. The increase in sEPSC frequency by VR1 onto midbrain dopaminergic neurons suggests the involvement of these receptors in motor and cognitive functions involving the dopaminergic system.

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“…All the enhancing or depressing effects of hypoglycemia on the agonist-induced currents (3 cells for each agonist) were reversible and were also observed in the presence of TTX (1 M, which was used to block fast sodium channel and synaptic transmission). In a series of experiments using the glutamate agonists, we also applied barium (300 M) to reduce either the potassium conductance increase caused by energy deprivation (Guatteo et al 1998a;Marinelli et al 2000;Mercuri et al 1994b) or the outward current that follows the application of the glutamate agonists (Mercuri et al 1996); under the treatment with this divalent cation, hypoglycemia enhanced NMDA, AMPA, and kainate responses and reduced the DHPG-induced inward current (2 neurons for each agonist). In addition, hypoglycemia did not cause changes of the I-V relationship of the currents caused by ionotropic ( Fig.…”

Section: Effects Of Hypoglycemia On the Agonist-mediated Responsesmentioning

confidence: 99%

Hypoglycemia Enhances Ionotropic But Reduces Metabotropic Glutamate Responses in Substantia Nigra Dopaminergic Neurons

Marinelli

Federici

Giacomini

et al. 2001

Journal of Neurophysiology

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It is widely accepted that energy deprivation causes a neuronal death that is mainly determined by an increase in the extracellular level of glutamate. Consequently an excessive membrane depolarization and a rise in the intracellular concentration of sodium and calcium are produced. In spite of this scenario, the function of excitatory and inhibitory amino acids during an episode of energy failure has not been studied yet at a cellular level. In a model of cerebral hypoglycemia in the rat substantia nigra pars compacta, we measured neuronal responses to excitatory amino acid agonists. Under single-electrode voltage-clamp mode at -60 mV, the application of the ionotropic glutamate receptor agonists N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate, and the metabotropic group I agonist (S)-3,5-dihydroxyphenilglycine (DHPG) produced reversible inward currents in the dopaminergic cells. In addition, an outward current was caused by the superfusion of the metabotropic GABA(B) agonist baclofen. Glucose deprivation enhanced the inward responses caused by each ionotropic glutamate agonist. In contrast, hypoglycemia depressed the DHPG-induced inward current and the baclofen-induced outward current. These effects of hypoglycemia were reversible. To test whether a failure of the Na(+)/K(+) ATPase pump could account for the modification of the agonist-induced currents during hypoglycemia, we treated the midbrain slices with strophanthidin (1-3 microM). Strophanthidin enhanced the inward currents caused by glutamate agonists. However, it did not modify the GABA(B)-induced outward current. Our data suggest that glucose deprivation enhances the inward current caused by the stimulation of ionotropic glutamate receptors while it dampens the responses caused by the activation of metabotropic receptors. Thus a substantial component of the augmented neuronal response to glutamate, during energy deprivation, is very likely due to the failure of Na(+) and Ca(2+) extrusion and might ultimately favor excitotoxic processes in the dopaminergic cells.

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Characterization of a Barium‐sensitive Outward Current following Glutamate Application on Rat Midbrain Dopaminergic Cells

Cited by 8 publications

References 44 publications

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Presynaptic Facilitation of Glutamatergic Synapses to Dopaminergic Neurons of the Rat Substantia Nigra by Endogenous Stimulation of Vanilloid Receptors

Hypoglycemia Enhances Ionotropic But Reduces Metabotropic Glutamate Responses in Substantia Nigra Dopaminergic Neurons

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