International Journal of Molecular Sciences

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Dr. Nina D. Anfinogenova

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Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, Russia
Interests: cardiology; biophysics; electrophysiology; intracellular signaling systems; ion transport; molecular biology; telemedicine; innovation; nanotechnology

Special Issue Information

Dear Colleagues,

Several gaseous molecules have been demonstrated as potential therapeutic, preventive, and diagnostic agents. Protocols of hundreds of clinical trials have been registered at ClinicalTrials.gov, suggesting a high implementation potential for gaseous agents. Administration of noble gases (He, Ar, and Xe), gas transmitters (CO, H₂S, and NO), and some other deliverable gases (H₂, O₂, O₃, and N₂O) result in the functional improvement in various organs and tissues. Xenon, argon, nitric oxide, carbon monoxide, and hydrogen sulfide exert putative neuroprotective and cardioprotective properties in different conditions ranging from cardiac-pulmonary bypass surgery and ischemia-reperfusion injury to alcohol-seeking behavior. The mechanistic basis of noble gas- and gas transmitter-medicated organ protection involves the modulation of oxidative stress, inflammatory responses, apoptotic processes, cell survival, and tissue repair. However, further efforts are needed to elucidate the entire spectrum of biological effects of gaseous molecules with promising therapeutic potential with especial attention to their possible toxicity and adverse reactions. Authors are invited to contribute to this Special Issue focusing on the mechanisms of protective effects exerted by gaseous molecules, their biological effects, signaling pathways, molecular targets, tissue distribution, biotransformation, preconditioning regimes, potential toxicity, and novel technologies of delivery.

Dr. Nina D. Anfinogenova
Guest Editor

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Keywords

noble gases
gas transmitters
cardiology
electrophysiology
neuroprotection
cardioprotection

Published Papers (2 papers)

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Research

16 pages, 5282 KiB

Open AccessArticle

Xenon’s Sedative Effect Is Mediated by Interaction with the Cyclic Nucleotide-Binding Domain (CNBD) of HCN2 Channels Expressed by Thalamocortical Neurons of the Ventrobasal Nucleus in Mice

by Nour El Dine Kassab, Verena Mehlfeld, Jennifer Kass, Martin Biel, Gerhard Schneider and Gerhard Rammes

Int. J. Mol. Sci. 2023, 24(10), 8613; https://doi.org/10.3390/ijms24108613 - 11 May 2023

Viewed by 1495

Abstract

Previous studies have shown that xenon reduces hyperpolarization-activated cyclic nucleotide-gated channels type-2 (HCN2) channel-mediated current (I_h) amplitude and shifts the half-maximal activation voltage (

V_{1 / 2}

) in thalamocortical circuits of acute brain slices to more hyperpolarized potentials. HCN2 [...] Read more.

V_{1 / 2}

) in thalamocortical circuits of acute brain slices to more hyperpolarized potentials. HCN2 channels are dually gated by the membrane voltage and via cyclic nucleotides binding to the cyclic nucleotide-binding domain (CNBD) on the channel. In this study, we hypothesize that xenon interferes with the HCN2 CNBD to mediate its effect. Using the transgenic mice model HCN2EA, in which the binding of cAMP to HCN2 was abolished by two amino acid mutations (R591E, T592A), we performed ex-vivo patch-clamp recordings and in-vivo open-field test to prove this hypothesis. Our data showed that xenon (1.9 mM) application to brain slices shifts the

V_{1 / 2}

of I_h to more hyperpolarized potentials in wild-type thalamocortical neurons (TC) (

V_{1 / 2}

: −97.09 [−99.56–−95.04] mV compared to control −85.67 [−94.47–−82.10] mV; p = 0.0005). These effects were abolished in HCN2EA neurons (TC), whereby the

V_{1 / 2}

reached only −92.56 [−93.16– −89.68] mV with xenon compared to −90.03 [−98.99–−84.59] mV in the control (p = 0.84). After application of a xenon mixture (70% xenon, 30% O₂), wild-type mice activity in the open-field test decreased to 5 [2–10] while in HCN2EA mice it remained at 30 [15–42]%, (p = 0.0006). In conclusion, we show that xenon impairs HCN2 channel function by interfering with the HCN2 CNBD site and provide in-vivo evidence that this mechanism contributes to xenon-mediated hypnotic properties. Full article

(This article belongs to the Special Issue Noble Gases and Gas Transmitters as Therapeutic and Preventive Molecules)

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16 pages, 4464 KiB

Open AccessArticle

Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve

by Kseniia Koroleva, Svetlana Svitko, Anton Ananev, Anastasiia Buglinina, Ksenia Bogatova, Olga Yakovleva, Dinara Nurmieva, Ilnar Shaidullov and Guzel Sitdikova

Int. J. Mol. Sci. 2023, 24(8), 7519; https://doi.org/10.3390/ijms24087519 - 19 Apr 2023

Cited by 3 | Viewed by 1367

Abstract

Nitric oxide is one of the endogenous molecules that play a key role in migraine. However, the interaction between NO and the main players in the nociceptive activity of the meningeal trigeminal afferents—TRPV1 and P2X3 receptors—remains unstudied. In the current project, the effects of acute and chronic NO administration on the activity of TRPV1 and P2X3 receptors in the peripheral afferents were studied using electrophysiological recording of action potentials of the trigeminal nerve in the rat hemiskull preparations. The data obtained indicate that exogenous and endogenous NO increased the activity of the trigeminal nerve independent on the inhibition of the TRPV1 and P2X3 receptors. The activity of the trigeminal nerve triggered by ATP changed neither in acute incubation in the NO donor—sodium nitroprusside (SNP) nor in the chronic nitroglycerine (NG)-induced migraine model. Moreover, the chronic NG administration did not increase in the number of degranulated mast cells in the rat meninges. At the same time, the capsaicin-induced activity of the trigeminal nerve was higher with chronic NO administration or after acute NO application, and these effects were prevented by N-ethylmaleimide. In conclusion, we suggested that NO positively modulates the activity of TRPV1 receptors by S-nitrosylation, which may contribute to the pro-nociceptive action of NO and underlie the sensitization of meningeal afferents in chronic migraine. Full article

(This article belongs to the Special Issue Noble Gases and Gas Transmitters as Therapeutic and Preventive Molecules)

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