Biology subjects

Ruiz-Suarez, J. C.

Publications and source records attributed to Ruiz-Suarez, J. C..

4 recordsLinked to original sources

bioRxiv2022

A high-cholesterol diet leads to faster induction of general anesthesia in two model animals: D. magna and C. elegans

General anesthesia (GA) has been under scientific scrutiny since its discovery more than a century ago, resulting in conceptually different proposed mechanisms to explain its origin and operation. Two mechanisms stand out: the lipid and the protein hypothesis. The Meyer-Overton rule (the more anesthetics dissolve in octanol, the greater their action) backups the first hypothesis, while the ligand-receptor interaction, specifically on ion channels, sustains the second. A recent study on Drosophila melanogaster draws attention to the possibility that both paradigms come together to explain GA synergistically, with the important caveat that this hybrid mechanism lies in the existence of lipid rafts in which cholesterol plays an essential role. Using two model organisms, the water flea (D. magna) and the nematode C. elegans, we give a further step to clarify this puzzle by carrying out anesthetic experiments with xenon and nitrous oxide. First, the obtained dose-response curves are very steep, implying that Hill coefficients greater than one are needed to describe them correctly, supporting an unspecific action mechanism. Second, we show that the animals response to both gases is influenced by a cholesterol diet modification, thus proving that this lipid promotes anesthetic induction. Our findings reenforce the idea that GA is driven by an allosteric induction rather than selective actions on single-target receptors.

neuroscience↗

bioRxiv2021

The effect of hydrophobic gases on the nervous system of Daphnia magna

Hundreds of hydrophobic substances: alkanes, alcohols, benzodiacepines, barbiturates, ethers and even gases, can induce General Anaesthesia (GA) in mammal animals. Moreover, it has been suggested that the primary site of action of such agents is on the spinal cord. Here, we investigate a scenario that is in double measure important to understand the mechanisms behind GA: its induction under water in invertebrate animals. We evaluate the capacity of xenon, nitrous oxide and krypton to suppress harmful sensations, provoked by intense light, in the crustacean D. magna. Due to the hydrophobic characteristics of those gases, we designed a special chamber to force them to dissolve in water at pressures up to to 50 atmospheres, whereas at the same time measure in real time the motility of the animals. Surprisingly, the aquatic animals are immobilized with xenon and nitrous oxide. Under this condition, they dont respond to a noxious stimulus. Our results are crucial to understand the action of inert gases in GA and the role of the spinal cord.

neuroscience↗

bioRxiv2021

The effect of hydrophobic gases on the nervous system of Daphnia magna

It is well known that some hydrophobic atomic and molecular gases provoke anaesthetic effects in mammal animals. Depending on the gas, there is a Minimum Alveolar Concentration (MAC) to produce anaesthesia. The gas enters in the lungs, dissolve in the blood and reaches the brain. Where are the targets and which are the action mechanisms are subjects not fully understood yet. Very recently, we reported the effects of local anaesthetics on the swimming behaviour of the water flea Daphnia magna (STOTEN 691, 278-283, 2019). Our aim now is to report new studies on the behaviour of this aquatic invertebrate in the presence of three hydrophobic gases: xenon, nitrous oxide and krypton. However, if local anaesthetics easily dissolve in water, these gases do not. Therefore, we designed a chamber to dissolve the gases using pressures up to 50 atmospheres. Simultaneously, we were able to measure in real time the response of the animals through transparent windows able to support such high pressures. Xenon and nitrous oxide effectively induce lack of movement in the daphnids. The effective pressures EP50 for xenon and nitrous oxide were and 5.2 atmospheres, respectively. Krypton does not present clear effects on the motile suppression, even after the exposure to 44 atmospheres. Our findings provide insight on the physiological effects important gases used in human medicine produce in aquatic invertebrate animals considered as potential models to study anesthesia.

neuroscience↗

bioRxiv2020

Cholesterol Sequestration by Xenon Leads to Lipid Raft Destabilization

Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and cholesterol (Chol). At a concentration of 2 Xe/lipid we observed an unexpected result: Spontaneous nucleation of Xe nanoclusters which then rapidly plunged into the bilayer. In this process Chol, essential for raft stabilization, was pulled out from the raft into the hydrophobic zone. When concentration was further increased (3 Xe/lipid), the clusters disrupted both the membrane and raft. We computed the radial distribution functions, pair-wise potentials, second virial coefficients and Schlit-ter entropy to scrutinize the nature of the interactions. Our findings suggest that the well-known anaesthetic effect of Xe could be mediated by sequestration of Chol, which, in turn, compromises the stability of rafts where specialized proteins needed to produce the nervous signal are anchored.

biophysics↗