L-glutamate and acetylcholine mobilise Ca2+ from the same intracellular pool in cerebellar granule cells using transduction mechanisms with different Ca2+ sensitivities

doi:10.1016/0143-4160(92)90064-Y

Cell Calcium

Volume 13, Issue 5, May 1992, Pages 293-301

https://doi.org/10.1016/0143-4160(92)90064-Y Get rights and content

Abstract

Ca²⁺ mobilisation induced by l-glutamate (Glu) and acetylcholine (ACh) has been studied in cultured cerebellar granule cells using digital fluorescence microscopy. The ability of Glu-receptor activation to mobilise Ca²⁺ was decreased when [Ca²⁺]_o was lowered to 10 μM (from 1.8 mM). It was enhanced when [Ca²⁺]_i was raised using 25 mM external K⁺ or by N-methyl-d-aspartate (NMDA), which selectively activates a distinct Glu-receptor subtype. The enhancement was dependent on entry of external Ca²⁺. In contrast, the ability of ACh receptor activation to mobilise Ca²⁺ was not affected by these conditions. Furthermore, pretreatment with pertussis toxin inhibited Ca²⁺ mobilisation in response to Glu-receptor activation without affecting mobilisation in response to ACh. However, activation of both receptors mobilised Ca²⁺ from a common, thapsigargin-sensitive pool. We conclude that there are differences in the Ca²⁺ mobilization pathways for the two receptor systems in cerebellar granule cells. The Ca²⁺-sensitivity of this Ca²⁺ mobilizing Glu receptor may have implications for its function in neuronal synaptogenesis and plasticity.

References (26)

F Nicoletti et al.
Pertussis toxin inhibits signal transduction at a specific metabotropic receptor in primary cultures of cerebellar granule cells
Neuropharmacology
(1988)
AJ Irving et al.
1S,3R-ACPD stimulates and L-AP3 blocks Ca²⁺ mobilization in rat cerebellar neurons
Eur. J. Pharmacol.
(1990)
G Grynkiewicz et al.
A new generation of Ca²⁺ indicators with greatly improved fluorescence properties
J. Biol. Chem.
(1985)
M Poenie
Alteration of intracellular Fura-2 fluorescence by viscosity: a simple correction
Cell Calcium
(1990)
E Palmer et al.
Glutamate receptors and phosphoinositide metabolism: stimulation via quisqualate receptors is inhibited by N-methyl-d-aspartate receptor activation
Mol. Brain Res.
(1988)
D-M Chuang
Neurotransmitter receptors and phosphoinositide turnover
Annu. Rev. Pharmacol. Toxicol.
(1989)
ML Mayer et al.
Excitatory amino acid receptors, second messengers and regulation of intracellular calcium in mammalian neurones
Trends. Pharmacol. Sci.
(1990)
JG Baird et al.
Role for ionotropic and metabotropic receptors in quisqualate stimulated inositol polyphosphate accumulation in rat cerebral cortex
Mol. Pharmacol.
(1991)
MP McCarthy et al.
The molecular biology of the acetylcholine receptor
Annu. Rev. Neurosci.
(1986)
DT Monaghan et al.
The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system
Annu. Rev. Pharmacol. Toxicol.
(1989)

O Manzoni et al.

(trans)-1-amino-cyclopentyl-1,3-dicarboxylate stimulates quisqualate phosphoinositide-coupled receptors but not ionotropic glutamate receptors in striatal neurones and Xenopus oocytes

Mol. Pharmacol.

(1990)

EM Whitman et al.

M₃ muscarinic cholinoceptors are linked to phosphoinositide metabolism in rat cerebellar granule cells

Eur. J. Pharmacol.

(1991)

V Gallo et al.

The role of depolarization in the survival and differentiation of cerebellar granule cells in culture

J. Neurosci.

(1987)

Cited by (68)

Neuronal differentiation of P19 embryonal carcinoma cells modulates kinin B2 receptor gene expression and function
2005, Journal of Biological Chemistry
Citation Excerpt :
The calcium response to the cholinergic agonist CCh was decreased by 90 and 50% on days 7 and 8, respectively, when cells had been differentiated in the presence of HOE-140 (1 μm) (Fig. 5, B and D). The CCh-induced rise in [Ca2+]i was confirmed to result from muscarinic, and not nicotinic, receptor activation, as the response was inhibited following pretreatment of the cells with thapsigargin (Fig. 5B) (37). Fig. 5E gives a quantification of Ca2+ responses upon stimulation of HOE-140-pretreated and control P19 cells on day 7 by BK or CCh.
Kinins are vasoactive oligopeptides generated upon proteolytic cleavage of low and high molecular weight kininogens by kallikreins. These peptides have a well established signaling role in inflammation and homeostasis. Nevertheless, emerging evidence suggests that bradykinin and other kinins are stored in the central nervous system and may act as neuromediators in the control of nociceptive response. Here we show that the kinin-B2 receptor (B2BKR) is differentially expressed during in vitro neuronal differentiation of P19 cells. Following induction by retinoic acid, cells form embryonic bodies and then undergo neuronal differentiation, which is complete after 8 and 9 days. Immunochemical staining revealed that B2BKR protein expression was below detection limits in nondifferentiated P19 cells but increased during the course of neuronal differentiation and peaked on days 8 and 9. Measurement of [Ca²⁺]_i in the absence and presence of bradykinin showed that most undifferentiated cells are unresponsive to bradykinin application, but following differentiation, P19 cells express high molecular weight neurofilaments, secrete bradykinin into the culture medium, and respond to bradykinin application with a transient increase in [Ca²⁺]_i. However, inhibition of B2BKR activity with HOE-140 during early differentiation led to a decrease in the size of embryonic bodies formed. Pretreatment of differentiating P19 cells with HOE-140 on day 5 resulted in a reduction of the calcium response induced by the cholinergic agonist carbamoylcholine and decreased expression levels of M1–M3 muscarinic acetylcholine receptors, indicating crucial functions of the B2BKR during neuronal differentiation.
The endoplasmic reticulum and neuronal calcium signalling
2002, Cell Calcium
The endoplasmic reticulum (ER) is a multifunctional signalling organelle regulating a wide range of neuronal functional responses. The ER is intimately involved in intracellular Ca²⁺ signalling, producing local or global cytosolic calcium fluctuations via Ca²⁺-induced Ca²⁺ release (CICR) or inositol-1,4,5-trisphosphate-induced Ca²⁺ release (IICR). The CICR and IICR are controlled by two subsets of Ca²⁺ release channels residing in the ER membrane, the Ca²⁺-gated Ca²⁺ release channels, generally known as ryanodine receptors (RyRs) and InsP₃-gated Ca²⁺ release channels, referred to as InsP₃-receptors (InsP₃Rs). Both types of Ca²⁺ release channels are expressed abundantly in nerve cells and their activation triggers cytoplasmic Ca²⁺ signals important for synaptic transmission and plasticity. The RyRs and InsP₃Rs show heterogeneous localisation in distinct cellular sub-compartments, conferring thus specificity in local Ca²⁺ signals. At the same time, the ER Ca²⁺ store emerges as a single interconnected pool fenced by the endomembrane. The continuity of the ER Ca²⁺ store could play an important role in various aspects of neuronal signalling. For example, Ca²⁺ ions may diffuse within the ER lumen with comparative ease, endowing this organelle with the capacity for “Ca²⁺ tunnelling”. Thus, continuous intra-ER Ca²⁺ highways may be very important for the rapid replenishment of parts of the pool subjected to excessive stimulation (e.g. in small compartments within dendritic spines), the facilitated removal of localised Ca²⁺ loads, and finally in conveying Ca²⁺ signals from the site of entry towards the cell interior and nucleus.
The endoplasmic reticulum as an integrating signalling organelle: From neuronal signalling to neuronal death
2002, European Journal of Pharmacology
The endoplasmic reticulum is one of the largest intracellular organelles represented by continuous network of cisternae and tubules, which occupies the substantial part of neuronal somatas and extends into finest neuronal processes. The endoplasmic reticulum controls protein synthesis as well as their post-translational processing, and generates variety of nucleus-targeted signals through Ca²⁺-binding chaperones. The normal functioning of the endoplasmic reticulum signalling cascades requires high concentrations of free calcium ions within the endoplasmic reticulum lumen ([Ca²⁺]_L), and severe alterations in [Ca²⁺]_L trigger endoplasmic reticulum stress response, manifested by either unfolded protein response (UPR) or endoplasmic reticulum overload response (EOR). At the same time, the endoplasmic reticulum is critically involved in fast neuronal signalling, by producing local or global cytosolic calcium signals via Ca²⁺-induced Ca²⁺ release (CICR) or inositol-1,4,5-trisphosphate-induced Ca²⁺ release (IICR). Both CICR and IICR are important for synaptic transmission and synaptic plasticity. Several special techniques allowing real-time [Ca²⁺]_L monitoring were developed recently. Video-imaging of [Ca²⁺]_L in neurones demonstrates that physiological signalling triggers minor decreases in overall intraluminal Ca²⁺ concentration due to strong activation of Ca²⁺ uptake, which prevents severe [Ca²⁺]_L alterations. The endoplasmic reticulum lumen also serves as a “tunnel” which allows rapid transport of Ca²⁺ ions within highly polarised nerve cells. Fluctuations of intraluminal free Ca²⁺ concentration represent a universal mechanism, which integrates physiological cellular signalling with protein synthesis and processing. In pathological conditions, fluctuations in [Ca²⁺]_L may initiate either adaptive or fatal stress responses.
Dual modulation of excitatory synaptic transmission by agonists at group I metabotropic glutamate receptors in the rat spinal dorsal horn
2000, Brain Research
Citation Excerpt :
In agreement with postsynaptic presence of both group I mGlu and NMDA receptors in the DH [46,58,89,94], a positive postsynaptic interaction between NMDA and group I mGlu receptors has been described in DH neurons [5,8,12,32,48,96]. Besides the mutual amplification of receptor function, the co-activation of NMDA and mGlu receptors may also result in the enhancement of the effects mediated by intracellular messengers, including calcium [13,42,63]. We have recently shown that DHPG increases NMDA-mediated Ca2+ transients in the substantia gelatinosa neurons [32].
The effects of group I metabotropic glutamate (mGlu) receptors on excitatory transmission in the rat dorsal horn, but mostly substantia gelatinosa, neurons were investigated using conventional intracellular recording in slices. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), the group I mGlu receptor selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG), and the selective mGlu subtype 5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), all induce long-lasting depression of A primary afferent fibers-mediated monosynaptic excitatory postsynaptic potential (EPSP), and long-lasting potentiation of polysynaptic EPSP, and EPSP in cells receiving C-afferent fiber input. The DHPG potentiation of polysynaptic EPSP was partially or fully reversed by (S)-4-carboxyphenylglycine (S-4CPG), the mGlu subtype 1 preferring antagonist. 2-Methyl-6-(phenylethynyl)-pyridine, the potent and selective mGlu subtype 5 antagonist, partially reversed the CHPG potentiation of polysynaptic EPSP. The effects of DHPG on monosynaptic and polysynaptic EPSPs were reduced, or abolished, by the N-methyl-d-aspartate (NMDA) receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (AP5). A clear and pronounced facilitation of the expression of DHPG- and CHPG-induced enhancement of polysynaptic EPSP, and EPSP evoked at C-fiber strength, was seen in the absence of gamma-aminobutyric acid subtype A receptor- and glycine-mediated synaptic inhibition. Besides dual modulation of excitatory synaptic transmission, DHPG induces depression of inhibitory postsynaptic potentials evoked by primary afferent stimulation in dorsal horn neurons. In addition, group I mGlu receptor agonists produced a direct persistent excitatory postsynaptic effect consisting of a slow membrane depolarization, an increase in input resistance, and an intense neuronal discharge. Cyclothiazide and (S)-4-CPG, the mGlu receptor subtype 1 preferring antagonists, significantly attenuated the DHPG-induced depolarization. These results demonstrate that the pharmacological activation of group I metabotropic glutamate receptors induces long-term depression (LTD) and long-term potentiation (LTP) of synaptic transmission in the spinal dorsal horn. These types of long-term synaptic plasticity may play a functional role in the generation of post-injury hypersensitivity (LTP) or antinociception (LTD).
Neuronal fast oscillations as a target site for psychoactive drugs
2000, Pharmacology and Therapeutics
Neuronal oscillations within the electroencephalogram β and γ bands (15–80 Hz) are associated with intense mental activity and cognitive function in general. Specifically, recent advances have implicated γ oscillations in the processing of sensory stimuli and demonstrated that synchronous γ oscillations, appearing concurrently in spatially separate brain regions, can induce β activity. β activity generated in this manner represents established synchronous communication between brain regions and is thought to represent a neuronal network correlate of the “binding phenomenon” in cognitive theory. This review will outline the mechanisms of generation of these oscillations at the cellular and network level, and will highlight the effects of drugs that may modify these mechanisms. Possible modification of fast oscillations by disease processes and clinical intervention are discussed.
Complex interactions between mGluRs, intracellular Ca<sup>2+</sup> stores and ion channels in neurons
2000, Trends in Neurosciences
Metabotropic glutamate receptors (mGluRs) can increase intracellular Ca²⁺ concentration via Ins(1,4,5)P₃- and ryanodine-sensitive Ca²⁺ stores in neurons. Both types of store are coupled functionally to Ca²⁺-permeable channels found in the plasma membrane. The mGluR-mediated increase in intracellular Ca²⁺ concentration can activate Ca²⁺-sensitive K⁺ channels and Ca²⁺-dependent nonselective cationic channels. These mGluR-mediated effects often result from mobilization of Ca²⁺ from ryanodine-sensitive, rather than Ins(1,4,5)P₃-sensitive, Ca²⁺ stores, suggesting that close functional interactions exist between mGluRs, intracellular Ca²⁺ stores and Ca²⁺-sensitive ion channels in the membrane.

View all citing articles on Scopus

View full text

L-glutamate and acetylcholine mobilise Ca2+ from the same intracellular pool in cerebellar granule cells using transduction mechanisms with different Ca2+ sensitivities

Abstract

Neuropharmacology

Eur. J. Pharmacol.

J. Biol. Chem.

Cell Calcium

Mol. Brain Res.

Neurotransmitter receptors and phosphoinositide turnover

Annu. Rev. Pharmacol. Toxicol.

Excitatory amino acid receptors, second messengers and regulation of intracellular calcium in mammalian neurones

Trends. Pharmacol. Sci.

Role for ionotropic and metabotropic receptors in quisqualate stimulated inositol polyphosphate accumulation in rat cerebral cortex

Mol. Pharmacol.

The molecular biology of the acetylcholine receptor

Annu. Rev. Neurosci.

The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system

Annu. Rev. Pharmacol. Toxicol.

(trans)-1-amino-cyclopentyl-1,3-dicarboxylate stimulates quisqualate phosphoinositide-coupled receptors but not ionotropic glutamate receptors in striatal neurones and Xenopus oocytes

Mol. Pharmacol.

M3 muscarinic cholinoceptors are linked to phosphoinositide metabolism in rat cerebellar granule cells

Eur. J. Pharmacol.

The role of depolarization in the survival and differentiation of cerebellar granule cells in culture

J. Neurosci.

L-glutamate and acetylcholine mobilise Ca²⁺ from the same intracellular pool in cerebellar granule cells using transduction mechanisms with different Ca²⁺ sensitivities

M₃ muscarinic cholinoceptors are linked to phosphoinositide metabolism in rat cerebellar granule cells