Calcium responses mediated by type 2 IP3-receptors are required for osmotic volume regulation of retinal glial cells in mice

Intracellular microelectrodes were used to examine the actions of pituitary adenylate cyclase-activating peptide (PACAP) on morphologically identified myenteric neurons and glial cells of the guinea pig small bowel. PACAP-27 and PACAP-38 evoked excitatory responses in 96% of after hyperpolarizing (AH)/type 2 neurons. The half-maximal concentration for PACAP-27 was 1.5 nM. The responses consisted of membrane depolarization in association with increased input resistance, suppression of hyperpolarizing afterpotentials, and repetitive spike discharge. Forskolin mimicked the action of PACAP in all AH/type 2 neurons. PACAP excited 36% of S/type 1 neurons. Most of the AH/type 2 neurons had Dogiel II morphology, whereas the S/type 1 neurons were uniaxonal with morphology characteristics of Dogiel I or filamentous neurons. No glial cells responded to PACAP. A selective A1 adenosine receptor agonist blocked the excitatory action of PACAP, and this was reversed by a selective A1 antagonist. The results suggest that excitatory PACAP receptors and inhibitory adenosine A1 receptors are linked to adenylate cyclase in AH/type 2 myenteric neurons.

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Glial Cells and Pro-inflammatory Cytokines as Shared Neurobiological Bases for Chronic Pain and Psychiatric Disorders

Overlapping Pain and Psychiatric Syndromes ◽

10.1093/med/9780190248253.003.0003 ◽

2020 ◽

pp. 27-49

Author(s):

Judith A. Strong ◽

Sang Won Jeon ◽

Jun-Ming Zhang ◽

Yong-Ku Kim

Keyword(s):

Chronic Pain ◽

Nervous System ◽

Psychiatric Disorders ◽

Inflammatory Cytokines ◽

Glial Cells ◽

Neuronal Excitability ◽

Pro Inflammatory Cytokines

This chapter reviews the roles of cytokines and glial cells in chronic pain and in psychiatric disorders, especially depression. One important role of cytokines is in communicating between activated glia and neurons, at all levels of the nervous system. This process of neuroinflammation plays important roles in pain and depression. Cytokines may also directly regulate neuronal excitability. Many cytokines have been implicated in both pain and psychiatric disorders, including interleukin-1β‎ (IL-1β‎), tumor necrosis factor-α‎, and IL-6. More generally, an imbalance between type 1, pro-inflammatory cytokines and type 2, anti-inflammatory cytokines has been implicated in both pain and psychiatric disorders. Activation of the sympathetic nervous system can contribute to both pain and psychiatric disorders, in part through its actions on inflammation and the cytokine profile.

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Differences in attachment between herpes simplex type 1 and type 2 viruses to neurons and glial cells

Infection and Immunity ◽

10.1128/iai.28.3.675-680.1980 ◽

1980 ◽

Vol 28 (3) ◽

pp. 675-680

Author(s):

A Vahlne ◽

B Svennerholm ◽

M Sandberg ◽

A Hamberger ◽

E Lycke

Keyword(s):

Herpes Simplex ◽

Glial Cells ◽

Binding Capacity ◽

No Adsorption ◽

Virus Binding ◽

Simplex Virus ◽

Astrocytic Glia ◽

Hsv 1

Fractions of nerve cell perikarya, synaptosomes, and astrocytic glia were prepared from human, monkey , rabbit, rat, and mouse brain tissue. The herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) binding capacity of these fractions was studied. Pretreatment of fractions with one type of HSV and the subsequent testing of adsorption of homotypic and heterotypic virus ws employed to reveal type selectivity of virus binding receptors. A higher density of HSV-1 than of HSV-2 selective receptors was found on synaptosomes and glial cells, except with mouse-derived preparations. Synaptosomal and glial cell preparations of mouse brains adsorbed both types of HSV well. Little or no adsorption was observed with HSV-1 and HSV-2 to neuronal perikarya. The type selectivity of HSV binding receptors on brain cells ws demonstrated on preparations of human synaptosomes and mouse glial cells. Some possible implications of the observations on the HSV infection of the nervous system are discussed.

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PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage

Development ◽

10.1242/dev.115.2.535 ◽

1992 ◽

Vol 115 (2) ◽

pp. 535-551 ◽

Cited By ~ 7

Author(s):

N.P. Pringle ◽

H.S. Mudhar ◽

E.J. Collarini ◽

W.D. Richardson

Keyword(s):

Glial Cells ◽

Receptor Expression ◽

Binding Studies ◽

Temporal And Spatial Distribution ◽

Inner Limiting Membrane ◽

Factor Alpha ◽

The Brain

Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) that contain mRNA encoding the platelet-derived growth factor alpha receptor (PDGF-alpha R). After embryonic day 16 (E16), PDGF-alpha R mRNA appears to be expressed by a subset of glial cells, but not by neurons. The temporal and spatial distribution of PDGF-alpha R+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-alpha R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. This conclusion is supported by the fact that the numbers of PDGF-alpha R+ cells in developing and adult optic nerves correlate well with independent estimates of the number of O-2A progenitor cells in the nerve at equivalent ages. Small numbers of PDGF-alpha R+ cells are present in the brain at E16, at which time they are found outside the subventricular germinal zones, suggesting that these cells do not express PDGF-alpha R until after, or shortly before they start to migrate away from the subventricular layer towards their final destinations. Reduced numbers of PDGF-alpha R+ cells persist in the adult CNS. PDGF-alpha R is also expressed strongly in the meningeal membranes and choroid plexus, and in the inner limiting membrane of the retina.

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Abstract 160: Contribution of IP3 Receptors in the Electromechanical Response of LV Myocytes to Gq-protein Coupled Receptor Agonists

Circulation Research ◽

10.1161/res.113.suppl_1.a160 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Sergio Signore ◽

Andrea Sorrentino ◽

Antonio Cannata ◽

Chiara Mangiaracina ◽

Mark Sundman ◽

...

Keyword(s):

Critical Role ◽

Resting Potential ◽

Ip3 Receptors ◽

Ip3 Receptor ◽

Electrical Stability ◽

Functional Responses ◽

Gpcr Activation ◽

Rna Targeting

Gq-protein coupled receptor (GPCR) stimulation promotes PLC function, generating diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). The latter may promote Ca2+ translocation from intracellular stores altering Ca2+ homeostasis in cardiomyocytes. The aim of this study was to establish whether GPCR agonists enhance IP3 receptor (IP3R) activity, affecting the electromechanical properties of LV myocytes. For this purpose, the functional responses of myocytes to GPCR agonists ATP or ET-1 were established. In field-stimulated cells, GPCR activators increased diastolic Ca2+, transient amplitude, and contractility; extra-systolic Ca2+ releases and aftercontractions were promoted. These responses were prevented by inhibition of PLC, or blockade of IP3Rs. Since DAG promotes PKC activity, the effects of GPCR stimulation were tested in the presence of the PKC inhibitor chelerythrine. This compound failed to abrogate the effects of ATP and ET-1, indicating that PKC-independent pathways play a critical role in mediating the observed cellular responses to GPCR stimulation. Additionally, an AAV9 vector carrying EGFP and sh-RNA targeting IP3R type-2 was employed in vivo to downregulate IP3Rs. GPCRs activation failed to increase Ca2+ transients and to induce extra-systolic Ca2+ elevations in EGFP-positive myocytes. Conversely, these responses were preserved in EGFP-negative cells. In patch-clamped myocytes, changes in Ca2+ transient properties following GPCR activation were accompanied by a decrease in resting potential, action potential (AP) prolongation, and emergence of arrhythmic events. Similar electrical disturbances were detected by direct activation of IP3R with IP3 dialysis, or by enhancing the affinity of the receptors to its ligand, with thimerosal. To establish whether Ca2+ mobilized from the sarcoplasmic reticulum (SR) to the cytoplasm via IP3Rs was responsible for the electrical alterations caused by GPCR agonists, experiments were performed in which SR Ca2+ was depleted, or cytosolic Ca2+ was buffered. Under these conditions, ATP and ET-1 failed to prolong the AP and to induce arrhythmias. In conclusion, the GPCR/IP3R axis regulates Ca2+ homeostasis, contractile performance and the electrical stability of LV myocytes.

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