Regulation of Intracellular Calcium in Cerebellar Granule Neurons: Effects of Depolarization and of Glutamatergic and Cholinergic Stimulation

Ciardo, Alberto; Meldolesi, Jacopo

doi:10.1111/j.1471-4159.1991.tb02579.x

Cited by 74 publications

(38 citation statements)

References 32 publications

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“…With intracellular recordings of striatal neurons, microiontophoretic applications of NMDA initiates spiking within a few hundred milliseconds of ejection current onset, and this is followed by a depolarization plateau upon which spikes with a decreased amplitude occur (Herrling et al, 1983;Cepeda et al, 1991). The initial burst of action potentials is likely mediated by Na ϩ and the longer lasting (several seconds) depolarized plateau is dependent on Ca 2ϩ currents (Herrling et al, 1983;Lambert et al, 1989;Cepeda et al, 1991;Ciardo and Meldolesi, 1991). In the present study, an apparent depolarization blockade was also observed with AMPA.…”

Section: Da Depletion Enhances Effects Of Nmda In Vp 379supporting

confidence: 69%

“…at ASPET Journals on May 12, 2018 jpet.aspetjournals.org inactivation induced acutely by EAA are not yet known, but alterations in Na ϩ and/or Ca 2ϩ conductance are likely candidates (Herrling et al, 1983;Lambert et al, 1989;Cepeda et al, 1991;Ciardo and Meldolesi, 1991). With intracellular recordings of striatal neurons, microiontophoretic applications of NMDA initiates spiking within a few hundred milliseconds of ejection current onset, and this is followed by a depolarization plateau upon which spikes with a decreased amplitude occur (Herrling et al, 1983;Cepeda et al, 1991).…”

Section: Da Depletion Enhances Effects Of Nmda In Vp 379mentioning

confidence: 99%

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Alterations in Responses of Ventral Pallidal Neurons to Excitatory Amino Acids after Long-Term Dopamine Depletion

Turner

Mignon²,

Napier³

2002

J Pharmacol Exp Ther

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The present study explored the possibility that excitatory amino acid (EAA) sensitivity within the ventral pallidum (VP) is altered by long-term removal of dopamine (DA). Electrophysiological experiments were conducted in chloral hydrate-anesthetized rats 21 to 28 days after they received unilateral substantia nigra injections of the dopaminergic toxin 6-hydroxydopamine (6-OHDA). VP neurons increased firing at low microiontophoretic ejection currents of the EAA agonists N-methyl-D-aspartate (NMDA) and ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA); however, high currents decreased action potential amplitude and rapidly caused cessation of neuronal firing. These responses likely reflected the induction of depolarization block for they were reversed by coiontophoresis of the hyperpolarizing transmitter ␥-aminobutyric acid (GABA) at ejection current levels that normally suppressed firing. The ability of NMDA and AMPA to induce such inactivation was greater in the VP of 6-OHDA-lesioned hemispheres, but unchanged in reserpinized rats, verifying that the alterations in responding to NMDA were the result of chronic, rather than acute, DA removal. The adaptations do not appear to be the consequence of a diminished GABAergic tone for the ability of bicuculline to increase firing (due to blocking a tonic GABAergic input) was not changed. However, low ejection currents of GABA that were insufficient to alter firing rate greatly attenuated the ability of NMDA to induce an apparent depolarization inactivation when coiontophoresed with NMDA onto VP neurons of the lesioned, but not the unlesioned, hemisphere. These studies show that chronic DA removal altered the EAA-induced amplitude-decreasing (i.e., the apparent depolarization inactivation) effects in VP neurons in the absence of a decrease in GABAergic tone.EAAs provide the major excitatory drive within the basal ganglia and limbic systems of the brain. Popular circuitry models for basal ganglia adaptations that accompany chronic near-total lesions of the ascending dopaminergic system incorporate the wealth of evidence for an up-regulation of EAA transmission (for review, see Ossowska, 1994). Moreover, suppression of EAA transmission by EAA antagonists attenuates motor dysfunction and augments the beneficial effects of levodopa in animal models of PD (Ossowska, 1994). The neuroanatomical substrates engaged by the up-regulation of EAA transmission in the DA-deafferented brain include those influenced by the enhancement in activity of STN EAAcontaining projections, e.g., the GPi (Brotchie et al., 1991;Filion and Tremblay, 1991) and the substantia nigra zona reticulata (Rohlfs et al., 1997).The VP receives direct innervation of EAA-containing afferents from limbic regions (e.g., amygdala; Russchen and Price, 1984;Maslowski-Cobuzzi and Napier, 1994) and the basal ganglia (e.g., STN;Groenewegen and Berendse, 1990;Turner et al., 2001). These inputs act on two major subtypes of ionotropic EAA receptors in the VP, NMDA, and non-NMDA (Monaghan and Cotman, 1985;...

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Section: Da Depletion Enhances Effects Of Nmda In Vp 379supporting

confidence: 69%

Section: Da Depletion Enhances Effects Of Nmda In Vp 379mentioning

confidence: 99%

Alterations in Responses of Ventral Pallidal Neurons to Excitatory Amino Acids after Long-Term Dopamine Depletion

Turner

Mignon²,

Napier³

2002

J Pharmacol Exp Ther

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“…Cerebellar granule cells possess a variety of receptors coupled to Ins(1,4,5)P3 generation, Ins(1,4,5)P3 receptors and the potential for second messenger-induced Ca2 + release from intracellular stores. It would seem probable therefore that the ability of 'metabotropic' excitatory amino acid, and perhaps muscarinic, agonists to release Ca2+ from intracellular stores of granule cells (Courtney et al, 1990;Irving et al, 1990;Ciardo & Meldolesi, 1991) involves this signalling sequence. The precise role(s) of Ins(1,4,5)P3-stimulated changes in intracellular Ca2+ concentration in excitable tissues is unknown.…”

Section: Discussionmentioning

confidence: 99%

Inositol 1,4,5‐trisphosphate‐stimulated calcium release from permeabilized cerebellar granule cells

Whitham

Challiss

Nahorski

1991

British J Pharmacology

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1 Muscarinic cholinoceptor stimulation of phosphoinositide hydrolysis in rat cultured cerebellar granule cells results in a rapid, transient accumulation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), which has been implicated in the release of non-mitochondrial intracellular Ca2+ stores. In the present study, the release of Ca2+ from intracellular stores and the Ins(1,4,5)P3 receptor responsible for this process have been investigated. 2 Monolayers of saponin-permeabilized granule cells accumulate 45Ca2 + in an ATP-dependent manner and the sequestered 45Ca2+ can be concentration-dependently released by Ins(1,4,5)P3 by a stereospecific and heparin-sensitive mechanism. The EC50 for Ins(1,4,5)P3-stimulated 45Ca2 + release was 80 + 3 nm.3 Radioligand binding studies performed on a crude granule cell membrane fraction indicated the presence of an apparently homogeneous population of stereo-specific Ins(1,4,5)P3 receptors (KD 54.7 + 2.0 nM; Bmax 1.37 + 0.29 pmol mg'-protein).4 This study provides evidence for Ins(1,4,5)P3-sensitive intracellular Ca2+ stores in primary cultures of cerebellar granule cells and suggest that these cells provide an excellent model neuronal system in which to study the relative functional roles of Ca2 + release from intracellular stores and Ca2 +-entry in neuronal Ca2+ homeostasis.

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“…Furthermore, studies on the mecha nism of neuronal death suggest that ischemia/hypoxia induced neuronal death is due to the release of glutamate (Glu) from brain tissue during hypoxia, and the excessive extracellular accumulation of Glu results in a Ca 21 over load which leads to neuronal degeneration (3 5). For these reasons, the direct effects of calcium antagonists which block the VOC and/or receptor operated calcium channel (ROC) may be beneficial and expected to improve the neuronal dysfunction either by blocking [Ca 21]i in crease or modulating Glu release (6).…”

mentioning

confidence: 99%

Effect of FK409, a Novel Nitric Oxide Donor, on Acute Experimental Myocardial Ischemia

Isono

Sato

Koibuchi

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The inhibitory effects of calcium antagonists on high-potassium or glutamate (Glu) enhanced intracellular calcium ion ([Ca2+];) levels were studied in cultured cerebellar granule cells. Dosages between 0.5 and 10 pM of flunarizine, nicardipine, SM6586 and SM12565 reduced the rise in [Ca 211i induced by 50 mM KC1 in a dose-dependent manner, although diltiazem, verapamil and nifedipine showed less effects on such [Ca 21]i increases. SM6586, SM12565 and flunarizine at dosages below 10 uM each reduced the magnitude of the [Ca2+]; increase induced by 25 pM Glu, but the other examined calcium antagonists were less effective. These results suggest the dissimilar efficacy of calcium antagonists on the inhibition of [Ca 21]i levels increased by high-potassium and Glu.

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Regulation of Intracellular Calcium in Cerebellar Granule Neurons: Effects of Depolarization and of Glutamatergic and Cholinergic Stimulation

Cited by 74 publications

References 32 publications

Alterations in Responses of Ventral Pallidal Neurons to Excitatory Amino Acids after Long-Term Dopamine Depletion

Alterations in Responses of Ventral Pallidal Neurons to Excitatory Amino Acids after Long-Term Dopamine Depletion

Inositol 1,4,5‐trisphosphate‐stimulated calcium release from permeabilized cerebellar granule cells

Effect of FK409, a Novel Nitric Oxide Donor, on Acute Experimental Myocardial Ischemia

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