scholarly journals Effect of Geraniol and Citronellol Essential Oils on the Biophysical Gating Properties of AMPA Receptors

2019 ◽  
Vol 9 (21) ◽  
pp. 4693 ◽  
Author(s):  
Mohammad Qneibi ◽  
Nidal Jaradat ◽  
Nour Emwas
Keyword(s):  
Essential Oils ◽  
Ampa Receptors ◽  
Neurological Diseases ◽  
Whole Cell Patch Clamp ◽  
293 Cells ◽  
Future Drug ◽  
Drug Synthesis ◽  
Patch Clamp Electrophysiology ◽  
Calming Effect ◽  
Natural Template

Essential oils have been advertised endlessly to be very beneficial for the health of humans, and an extensive amount of research examines the validity of such claims. In contribution, the current study evaluates the neuroprotective properties of Citronellol and Geraniol essential oils (EOs). In relationship to the biophysical gating properties of different the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, the EOs were administered to HEK293 (Human embryonic kidney 293) cells and examined for any inhibition and effect on desensitization or deactivation rates, using whole-cell patch-clamp electrophysiology. Our results demonstrated the highest levels of inhibition from Citronellol oil by four-fold on all AMPARs subunits. Likewise, Geraniol oil had a similar inhibiting impact on the receptors, and both oils decreased the desensitization and deactivation rates of the inhibited receptors. Thus, the examined EOs of this study portray neuroprotective qualities by targeting AMPARs activation and reducing desensitization and deactivation rates. Finally, the results of the current study entail a better understanding of AMPARs, provides a natural template for future drug synthesis to treat neurological diseases associated with excessive AMPAR activation, and offers a possible mechanism by which these essential oils deploy their ‘calming’ effect.

scholarly journals The Neuroprotective Role of Origanum syriacum L. and Lavandula dentata L. Essential Oils through Their Effects on AMPA Receptors

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Qneibi ◽  
Nidal Jaradat ◽  
Mohammed Hawash ◽  
Abdel Naser Zaid ◽  
Abdel-Razzak Natsheh ◽  
...  
Keyword(s):  
Essential Oils ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Neurological Diseases ◽  
Critical Role ◽  
Hek293 Cells ◽  
Gas Chromatography Mass Spectrometry ◽  
Active Components ◽  
Study Results ◽  
Kinetics Of

Lavandula dentata L. and Origanum syriacum L. essential oils have numerous health benefits and properties, such as possessing common components with a variant degree of depressive actions in the central nervous system. We investigated the depressive property of these oils on AMPA receptors, which are responsible for most of the fast-excitatory neurotransmission in the CNS and play a critical role in synaptic plasticity. Since excessive activation of AMPARs has been linked to neurotoxicity leading to various pathologies, we hypothesize that these oils have a neuroprotective role by acting directly on the kinetics of AMPARs. Using Gas Chromatography-Mass Spectrometry (GC/MS) and patch-clamp electrophysiology, the essential oils of L. dentata flowers and O. syriacum leaves were characterized and the whole cell currents were measured with and without the administration of the oils onto HEK293 cells. The current study results showed that the biophysical properties of AMPA receptor subunits showed a decrease in desensitization rate of GluA1 and GluA2 homomers, using O. syriacum, while administering L. dentata oil decreased the desensitization rate of GluA1 and GluA2 homomers, as well as GluA1/2 heteromers. As for the deactivation rate, both oils slowed the deactivation kinetics of all AMPA receptor subunits. Intriguingly, between the two oils, the effect of desensitization and deactivation was of a greater significance for L. dentata oil than O. syriacum. Our data suggest that the two oils contain components that are essential to identify, as those active components underlie the oils’ neuronal depressive properties reported, and to extract them to synthesize a potent neuroprotective drug to treat neurological diseases potentially.

scholarly journals Discovery, Pharmacological Characterisation and NMR Structure of the Novel µ-Conotoxin SxIIIC, a Potent and Irreversible NaV Channel Inhibitor

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 391 ◽  
Author(s):  
Kirsten L. McMahon ◽  
Hue N.T. Tran ◽  
Jennifer R. Deuis ◽  
Richard J. Lewis ◽  
Irina Vetter ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Solution Structure ◽  
Neurological Diseases ◽  
The Novel ◽  
Cone Snail ◽  
Whole Cell Patch Clamp ◽  
Channel Selectivity ◽  
Patch Clamp Electrophysiology ◽  
Α Helix ◽  
Drug Leads

Voltage-gated sodium (NaV) channel subtypes, including NaV1.7, are promising targets for the treatment of neurological diseases, such as chronic pain. Cone snail-derived µ-conotoxins are small, potent NaV channel inhibitors which represent potential drug leads. Of the 22 µ-conotoxins characterised so far, only a small number, including KIIIA and CnIIIC, have shown inhibition against human NaV1.7. We have recently identified a novel µ-conotoxin, SxIIIC, from Conus striolatus. Here we present the isolation of native peptide, chemical synthesis, characterisation of human NaV channel activity by whole-cell patch-clamp electrophysiology and analysis of the NMR solution structure. SxIIIC displays a unique NaV channel selectivity profile (1.4 > 1.3 > 1.1 ≈ 1.6 ≈ 1.7 > 1.2 >> 1.5 ≈ 1.8) when compared to other µ-conotoxins and represents one of the most potent human NaV1.7 putative pore blockers (IC50 152.2 ± 21.8 nM) to date. NMR analysis reveals the structure of SxIIIC includes the characteristic α-helix seen in other µ-conotoxins. Future investigations into structure-activity relationships of SxIIIC are expected to provide insights into residues important for NaV channel pore blocker selectivity and subsequently important for chronic pain drug development.

An Extrasynaptic GABAA Receptor Mediates Tonic Inhibition in Thalamic VB Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 4491-4501 ◽  
Author(s):  
Fan Jia ◽  
Leonardo Pignataro ◽  
Claude M. Schofield ◽  
Minerva Yue ◽  
Neil L. Harrison ◽  
...  
Keyword(s):  
Critical Role ◽  
Brain Slices ◽  
Oscillatory Activity ◽  
Thalamic Neurons ◽  
Hek 293 ◽  
Subunit Protein ◽  
Whole Cell Patch Clamp ◽  
293 Cells ◽  
Hypnotic Agent ◽  
Tonic Current

Whole cell patch-clamp recordings were obtained from thalamic ventrobasal (VB) and reticular (RTN) neurons in mouse brain slices. A bicuculline-sensitive tonic current was observed in VB, but not in RTN, neurons; this current was increased by the GABAA receptor agonist 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridine-3-ol (THIP; 0.1 μM) and decreased by Zn2+ (50 μM) but was unaffected by zolpidem (0.3 μM) or midazolam (0.2 μM). The pharmacological profile of the tonic current is consistent with its generation by activation of GABAA receptors that do not contain the α1 or γ2 subunits. GABAA receptors expressed in HEK 293 cells that contained α4β2δ subunits showed higher sensitivity to THIP (gaboxadol) and GABA than did receptors made up from α1β2δ, α4β2γ2s, or α1β2γ2s subunits. Western blot analysis revealed that there is little, if any, α3 or α5 subunit protein in VB. In addition, co-immunoprecipitation studies showed that antibodies to the δ subunit could precipitate α4, but not α1 subunit protein. Confocal microscopy of thalamic neurons grown in culture confirmed that α4 and δ subunits are extensively co-localized with one another and are found predominantly, but not exclusively, at extrasynaptic sites. We conclude that thalamic VB neurons express extrasynaptic GABAA receptors that are highly sensitive to GABA and THIP and that these receptors are most likely made up of α4β2δ subunits. In view of the critical role of thalamic neurons in the generation of oscillatory activity associated with sleep, these receptors may represent a principal site of action for the novel hypnotic agent gaboxadol.

scholarly journals Zn2+ Slows Down CaV3.3 Gating Kinetics: Implications for Thalamocortical Activity

2007 ◽  
Vol 98 (4) ◽  
pp. 2274-2284 ◽  
Author(s):  
M. Cataldi ◽  
V. Lariccia ◽  
V. Marzaioli ◽  
A. Cavaccini ◽  
G. Curia ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Whole Cell ◽  
Hek 293 ◽  
Gating Kinetics ◽  
Epileptiform Discharges ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation ◽  
293 Cells ◽  
Channel Opening ◽  
Current Activation

We employed whole cell patch-clamp recordings to establish the effect of Zn2+ on the gating the brain specific, T-type channel isoform CaV3.3 expressed in HEK-293 cells. Zn2+ (300 μM) modified the gating kinetics of this channel without influencing its steady-state properties. When inward Ca2+ currents were elicited by step depolarizations at voltages above the threshold for channel opening, current inactivation was significantly slowed down while current activation was moderately affected. In addition, Zn2+ slowed down channel deactivation but channel recovery from inactivation was only modestly changed. Zn2+ also decreased whole cell Ca2+ permeability to 45% of control values. In the presence of Zn2+, Ca2+ currents evoked by mock action potentials were more persistent than in its absence. Furthermore, computer simulation of action potential generation in thalamic reticular cells performed to model the gating effect of Zn2+ on T-type channels (while leaving the kinetic parameters of voltage-gated Na+ and K+ unchanged) revealed that Zn2+ increased the frequency and the duration of burst firing, which is known to depend on T-type channel activity. In line with this finding, we discovered that chelation of endogenous Zn2+ decreased the frequency of occurrence of ictal-like epileptiform discharges in rat thalamocortical slices perfused with medium containing the convulsant 4-aminopyridine (50 μM). These data demonstrate that Zn2+ modulates CaV3.3 channel gating thus leading to increased neuronal excitability. We also propose that endogenous Zn2+ may have a role in controlling thalamocortical oscillations.

scholarly journals Current injection and receptor-mediated excitation produce similar maximal firing rates in hypoglossal motoneurons

2016 ◽  
Vol 115 (3) ◽  
pp. 1307-1313 ◽  
Author(s):  
Hilary E. Wakefield ◽  
Ralph F. Fregosi ◽  
Andrew J. Fuglevand
Keyword(s):  
Time Course ◽  
Input Resistance ◽  
Current Injection ◽  
Synaptic Activity ◽  
High Concentration ◽  
Membrane Potential Change ◽  
Firing Rates ◽  
Whole Cell Patch Clamp ◽  
Patch Clamp Electrophysiology ◽  
High Firing

The maximum firing rates of motoneurons (MNs), activated in response to synaptic drive, appear to be much lower than that elicited by current injection. It could be that the decrease in input resistance associated with increased synaptic activity (but not current injection) might blunt overall changes in membrane depolarization and thereby limit spike-frequency output. To test this idea, we recorded, in the same cells, maximal firing responses to current injection and to synaptic activation. We prepared 300 μm medullary slices in neonatal rats that contained hypoglossal MNs and used whole-cell patch-clamp electrophysiology to record their maximum firing rates in response to triangular-ramp current injections and to glutamate receptor-mediated excitation. Brief pressure pulses of high-concentration glutamate led to significant depolarization, high firing rates, and temporary cessation of spiking due to spike inactivation. In the same cells, we applied current clamp protocols that approximated the time course of membrane potential change associated with glutamate application and with peak current levels large enough to cause spike inactivation. Means (SD) of maximum firing rates obtained in response to glutamate application were nearly identical to those obtained in response to ramp current injection [glutamate 47.1 ± 12.0 impulses (imp)/s, current injection 47.5 ± 11.2 imp/s], even though input resistance was 40% less during glutamate application compared with current injection. Therefore, these data suggest that the reduction in input resistance associated with receptor-mediated excitation does not, by itself, limit the maximal firing rate responses in MNs.

scholarly journals Hyperexcitability and loss of feedforward inhibition in the Fmr1KO lateral amygdala

2020 ◽  
Author(s):  
E. Mae Guthman ◽  
Matthew N. Svalina ◽  
Christian A. Cea-Del Rio ◽  
J. Keenan Kushner ◽  
Serapio M. Baca ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Fragile X ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Excitatory Synapses ◽  
Lateral Amygdala ◽  
Early Postnatal Development ◽  
Whole Cell Patch Clamp ◽  
Patch Clamp Electrophysiology

SummaryFragile X Syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disability, autism spectrum disorders (ASDs), and anxiety disorders. The disruption in the function of the FMR1 gene results in a range of alterations in cellular and synaptic function. Previous studies have identified dynamic alterations in inhibitory neurotransmission in early postnatal development in the amygdala of the mouse model of FXS. Yet little is known how these changes alter microcircuit development and plasticity in the lateral amygdala (LA). Using whole-cell patch clamp electrophysiology, we demonstrate that principal neurons (PNs) in the LA exhibit hyperexcitability with a concomitant increase in the synaptic strength of excitatory synapses in the BLA. Further, reduced feed-forward inhibition appears to enhance synaptic plasticity in the FXS amygdala. These results demonstrate that plasticity is enhanced in the amygdala of the juvenile Fmr1 KO mouse and that E/I imbalance may underpin anxiety disorders commonly seen in FXS and ASDs.

scholarly journals Roll on Aromaterapy Formula Activity Test Essential Oil Syzygium aromaticum L.

2020 ◽  
Vol 2 (3) ◽  
pp. 265-270
Author(s):  
Ariyanti Ariyanti ◽  
Eni Masruriati ◽  
Mazikhatul Azka ◽  
Arini Asna Hidayah
Keyword(s):  
Experimental Design ◽  
Essential Oil ◽  
Essential Oils ◽  
Syzygium Aromaticum ◽  
Activity Test ◽  
Soxhlet Method ◽  
Calming Effect ◽  
And Control

Syzygium aromaticum L. is a plant that contains essential oils. The essential oil of the clove plant is produced from the distillation of Syzygium aromaticum L.s, stalks, and leaves. The components of Syzygium aromaticum L. content are eugenol, eugenol acetate and cariophylene. The specifications of each part of the essential oil of Syzygium aromaticum L. (21.3%), eugenol (78-95%) using the Soxhlet method were about 47.57%. The purpose of this study was to determine the activity and effectiveness of the roll on formulation of Syzygium aromaticum L. essential oil. This study was experimental with the experimental design used was the posttest only controlled group. The research object was divided into two groups of treatment and control. The results showed that the roll on formulation of Syzygium aromaticum L. essential oil had a calming effect on mice. The most effective roll on formulation of Syzygium aromaticum L. essential oil is 7% concentration.

scholarly journals High frequency neuronal bursting is essential for circadian and sleep behaviors in Drosophila

2020 ◽  
Author(s):  
Florencia Fernandez-Chiappe ◽  
Lia Frenkel ◽  
Carina Celeste Colque ◽  
Ana Ricciuti ◽  
Bryan Hahm ◽  
...  
Keyword(s):  
High Frequency ◽  
Firing Pattern ◽  
Genetic Screen ◽  
Temporal Organization ◽  
Neuropeptide Release ◽  
Cation Current ◽  
Bursting Neurons ◽  
Whole Cell Patch Clamp ◽  
Pattern Characteristic ◽  
Patch Clamp Electrophysiology

AbstractCircadian rhythms have been extensively studied in Drosophila, however, still little is known about how the electrical properties of clock neurons are specified. We have performed a behavioral genetic screen through the downregulation of candidate ion channels in the lateral ventral neurons (LNvs) and show that the hyperpolarization-activated cation current Ih is important for the behaviors that the LNvs command: temporal organization of locomotor activity and sleep. Using whole-cell patch clamp electrophysiology we demonstrate that small LNvs are bursting neurons, and that Ih is necessary to achieve the high frequency bursting firing pattern characteristic of both types of LNvs. Since firing in bursts has been associated to neuropeptide release, we hypothesized that Ih would be important for LNvs communication. Indeed, herein we demonstrate that Ih is fundamental for the recruitment of PDF filled dense core vesicles to the terminals at the dorsal protocerebrum and for their timed release, and hence for the temporal coordination of circadian behaviors.

scholarly journals Characterization of α3 Glycine Receptors with Ginkgolide B and Picrotoxin

2018 ◽  
Author(s):  
Sampurna Chakrabarti ◽  
Anil Neelakantan ◽  
Malcolm M. Slaughter
Keyword(s):  
Beta Subunits ◽  
Ginkgolide B ◽  
Glycine Receptors ◽  
Hek 293 ◽  
Whole Cell Patch Clamp ◽  
293 Cells ◽  
Voltage Dependent ◽  
The Central Nervous System ◽  
Subunit Isoforms

AbstractGinkgolide B (GB) and picrotoxin (PTX) are antagonists of the major inhibitory receptors of the central nervous system: GABA and glycine receptors (GlyRs). GlyRs contain one or more of the four alpha subunit isoforms of which α1 and α2 have been extensively studied. This report compares GB and PTX block of α3 GlyRs expressed in HEK 293 cells, using whole-cell patch clamp techniques. In CNS, α3 exists as a heteropentamer in conjunction with beta subunits in a 2α:3β ratio. Thus, the nature of block was also tested in α3β heteromeric glycine receptors. GB and PTX blocked α3 GlyRs both in the presence (liganded state) and absence of glycine (unliganded state). This property is unique to α3 subunits; α1 and α2 subunits are only blocked in the liganded state. The GB block of α3 GlyRs is voltage-dependent (more effective when the cell is depolarized) and non-competitive, while the PTX block is competitive and not voltage-dependent. The heteromeric and homomeric α3 GlyRs recovered significantly faster from unliganded GB block compared to liganded GB block, but no such distinction was found for PTX block suggesting more than one binding site for GB. This study sheds light on features of the α3 GlyR that distinguish it from the more widely studied α1 and α2 subunits. Understanding these properties can help decipher the physiological functioning of GlyRs in the CNS and may permit development of subunit specific drugs.

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