pH-dependent modulation of N-methyl-d-aspartate receptor-mediated synaptic currents by histamine in rat hippocampus in vitro

doi:10.1016/0304-3940(95)12051-5

Neuroscience Letters

Volume 199, Issue 3, 27 October 1995, Pages 225-227

https://doi.org/10.1016/0304-3940(95)12051-5 Get rights and content

Abstract

Modulation of excitatory postsynaptic currents by histamine was examined using whole cell recording methods in the CA1 region of slices of rat hippocampus. Histamine affected the N-methyl-d-aspartate (NMDA) component of the synaptic current in a pHdependent manner: at lowered pH (7.2) it enhanced the NMDA-mediated synaptic currents while at raised pH (7.6) it reduced them. At a pH of 7.4 there was no significant action of histamine. Histamine failed to alter the non-NMDA component of the synaptic current. These results indicate that histamine acts at a, postsynaptic site to modulate NMDA mediated synaptic currents in a pH dependent manner. This mechanism may have important implications for the pathophysiology of shifts in extracellular pH.

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Cited by (25)

The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus
2015, Neuropharmacology
Citation Excerpt :
Histamine has been reported to potentiate N-Methyl-d-Aspartate (NMDA) currents by a direct interaction with NMDA receptors (Vorobjev et al., 1993). This effect depends on the concentration of histamine (Burban et al., 2010) and pH (Saybasili et al., 1995). It is possible that the changes in intracellular and extracellular pH during seizure activity (Xiong and Stringer, 2000; Helmy et al., 2012) facilitate the histamine-induced potentiation of NMDA currents and the subsequent neuronal damage.
Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.
Histamine Influences the Blood-Spinal Cord and Brain Barriers Following Injuries to the Central Nervous System
2004, Blood-Spinal Cord and Brain Barriers in Health and Disease
Influence of histamine in central nervous system (CNS) injury is not well known. New evidence suggests that histamine modulates signal–transducing mechanisms in the cerebral capillaries that can be primarily responsible for breakdown of the microvascular barriers, causing vasogenic edema formation and brain pathology. This chapter reviews the role of histamine on the blood–spinal cord and brain barriers following several kinds of CNS insults. Using pharmacological approaches it appears that the histamine can be regarded as one of the important neurotransmitters influencing pathophysiology of the cerebrovascular barriers and nerve cell injuries. New therapeutic potentials of histamine agonists and antagonists to attenuate the pathophysiology of CNS injuries are discussed.
The physiology of brain histamine
2001, Progress in Neurobiology
Histamine-releasing neurons are located exclusively in the TM of the hypothalamus, from where they project to practically all brain regions, with ventral areas (hypothalamus, basal forebrain, amygdala) receiving a particularly strong innervation. The intrinsic electrophysiological properties of TM neurons (slow spontaneous firing, broad action potentials, deep afterhyperpolarisations, etc.) are extremely similar to other aminergic neurons. Their firing rate varies across the sleep-wake cycle, being highest during waking and lowest during rapid-eye movement sleep. In contrast to other aminergic neurons somatodendritic autoreceptors (H₃) do not activate an inwardly rectifying potassium channel but instead control firing by inhibiting voltage-dependent calcium channels. Histamine release is enhanced under extreme conditions such as dehydration or hypoglycemia or by a variety of stressors. Histamine activates four types of receptors. H₁ receptors are mainly postsynaptically located and are coupled positively to phospholipase C. High densities are found especially in the hypothalamus and other limbic regions. Activation of these receptors causes large depolarisations via blockade of a leak potassium conductance, activation of a non-specific cation channel or activation of a sodium–calcium exchanger. H₂ receptors are also mainly postsynaptically located and are coupled positively to adenylyl cyclase. High densities are found in hippocampus, amygdala and basal ganglia. Activation of these receptors also leads to mainly excitatory effects through blockade of calcium-dependent potassium channels and modulation of the hyperpolarisation-activated cation channel. H₃ receptors are exclusively presynaptically located and are negatively coupled to adenylyl cyclase. High densities are found in the basal ganglia. These receptors mediated presynaptic inhibition of histamine release and the release of other neurotransmitters, most likely via inhibition of presynaptic calcium channels. Finally, histamine modulates the glutamate NMDA receptor via an action at the polyamine binding site. The central histamine system is involved in many central nervous system functions: arousal; anxiety; activation of the sympathetic nervous system; the stress-related release of hormones from the pituitary and of central aminergic neurotransmitters; antinociception; water retention and suppression of eating. A role for the neuronal histamine system as a danger response system is proposed.
Inositol 1,4,5-trisphosphate-sensitive Ca<sup>2+</sup> stores in rat supraoptic neurons: Involvement in histamine-induced enhancement of depolarizing afterpotentials
1999, Neuroscience
Histamine, a putative neuromodulator and neurotransmitter, can depolarize supraoptic neurons and enhance depolarizing afterpotentials that play a key role in determining the excitability of these neurons. This study investigated intracellular signal transduction involved in histamine-induced enhancement of depolarizing afterpotentials utilizing immunohistochemical and electrophysiological methods. Abundant inositol 1,4,5-trisphosphate receptor-related immunostaining was seen in all parts of the supraoptic nucleus, mainly within somata and proximal processes of the magnocellular neurons, but also in astrocytes of the ventral glial lamina. In supraoptic neurons displaying depolarizing afterpotentials, three brief depolarizations evoked a slow inward current. Bath application of histamine (1–2.5 μM) reversibly enhanced this slow inward current in almost all supraoptic neurons tested. Amplitudes and durations of the slow inward current were increased by 68.1% and 22.8%, respectively. Pretreatment of cells with a histamine receptor (subtype 1) antagonist (pyrilamine) or inhibitors of phospholipase C activation (neomycin or U73122) prevented histamine-induced enhancement of the slow inward current. When electrodes containing heparin, an inositol 1,4,5-trisphosphate receptor blocker, were used for recording, histamine had no effect on the slow inward current. Heparin, however, failed to abolish norepinephrine-induced enhancement of the slow inward current. After H₇ [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], an inhibitor of protein kinase C, was infused into supraoptic neurons via the electrodes, histamine-induced enhancement of the slow inward current was also blocked.
These results indicate the presence of, and functional roles for, inositol 1,4,5-trisphosphate receptor-sensitive Ca²⁺ stores in supraoptic neurons. Following activation of histamine receptors (subtype 1) and phospholipase C, Ca²⁺ mobilization from internal stores participates in mediating histamine-induced enhancement of depolarizing afterpotentials.
The protective role of mild acidic pH shifts on synaptic NMDA current in hippocampal slices
1998, Brain Research
Glutamate is a major neurotransmitter in the CNS. Its release activates NMDA and non-NMDA receptors on the postsynaptic membrane. NMDA receptor activation is shown to be important in physiological and pathological events. The modulatory sites on the NMDA receptor-channel ionophore complex are important in the regulation of the channel's cation conductance. Regulation of the channel by proton concentration may be important in the alkalinization that occurs during the normal release of glutamate or in the acidification that occurs during hypoxia/ischemia. In this study, the selective downregulation of the NMDA channel with slight extracellular pH changes and reversibility of this modulation have been shown in hippocampal slices. It has also been shown that hippocampal slices are more responsive to pH changes than other experimental preparations. The downregulation of the NMDA current may represent a native control mechanism. Direct and indirect modulation caused by extracellular pH changes on the NMDA receptor ionophore complex might be important in the overall response of the neuron under pathophysiological changes.
Long-term increase of hippocampal excitability by histamine and cyclic AMP
1997, Neuropharmacology
The action of histamine (HA) on rat hippocampal CA1 pyramidal cells in vitro was investigated in slices perfused with solution containing $0.2 mM Ca^{2+} 4.0 mM Mg^{2+}$ . Extracellular recordings of the spontaneous discharges occurring under these conditions revealed that HA caused a long-lasting increase in cell firing. The HA-effects were dose-dependent, in that low concentrations of HA (0.1–0.5 μM) exhibited an initial transient depression of cell firing and practically no long-lasting action, whereas higher concentrations of HA (1–10 μM) exerted strong, non-declining increases. The H₁-receptor antagonist mepyramine (1 μM) blocked the initial depression of firing and attenuated the long-lasting HA-mediated excitation. Pure H₁-receptor activation, tested with the H₁-receptor agonist 2-(3-fluorphenyl)histamine (1–10 μM) depressed cell firing, similar to the low dose effects of HA. HA-induced excitations were prevented by the H₂-receptor antagonist cimetidine (10–50 μM), and mimicked by the very potent H₂-receptor agonist impromidine (1 or 3 μM) which was, however, less effective compared to equal concentrations of HA. H₃-receptor activation by R-α-methylhistamine had no significant effect on cell firing. Thus, histamine H₁ and H₂ receptors seem to cooperate in producing this long-lasting augmentation of excitability. 8-Bromo-cyclic AMP monophosphate (8-Br-cAMP, 50–100 μM) mimicked the long-term excitation, whereas the adenylyl-cyclase inhibitor 9-tetrahydro-2-furyladenine (THFA, 100–500 μM) or the PKA-inhibitor Rp-adenosine-3′5′-cyclic monophosphate (Rp-cAMPS, 10 μM) blocked it, indicating that the HA-mediated increase of excitability in the hippocampus is dependent on the adenylate cyclase/PKA-signal transduction cascade. dl-2-Amino-5-phosphonopentanoic acid (APV, 50 μM) significantly attenuated the magnitude of the HA-induced enhancement, indicating an NMDA receptor-dependent component. Other biogenic amines, acting through receptors positively coupled to adenylyl cyclase, elicited similar responses as HA, indicating common mechanisms by which these substances modulate excitability in CA1 pyramidal cells.

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pH-dependent modulation of N-methyl-d-aspartate receptor-mediated synaptic currents by histamine in rat hippocampus in vitro

Abstract

Neuron

Brain Res.

Neuron

Neuron

Enhancement by histamine of NMDA-mediated synaptic transmission in the hippocampus

Science

Effects of histamine on hippocampal pyramidal cells of the rat in vitro

Exp. Brain Res.

Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells

Nature