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Ion Channels and Synaptic Transmission in the Differrent Phases of...
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Ion Channels and Synaptic Transmission in the Differrent Phases of Life

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Biochemistry, Biophysics and Computational Biology".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 8682

Special Issue Editors

Dr. Francesca Grassi

E-Mail Website
Guest Editor
Department of Physiology and Pharmacology, University of Rome "La Sapienza", 00185 Rome, Italy
Interests: functional properties of nicotinic acetylcholine receptors; biological effects of random signals; computational approaches to disease progression
Dr. Maria Amalia Di Castro

E-Mail Website
Guest Editor
Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy
Interests: synaptic transmission; glia-neuron communication; plasticity; chemokines; neurological disorders

Special Issue Information

Dear colleagues,

ION channels are key determinants of cell functions and interactions with the environment, regulating phenomena as diverse as cell motility, muscle contraction and synaptic transmission. It is therefore not surprising that, in all phases of life, from development to adulthood and aging, ion channels contribute to set the status of an individual in the continuum between strong health and marked pathology. On the other hand, the developmental stage or health status of a subject regulates the expression, structure and function of many ion channels in several cell types.

In this special issue, we aim at collecting examples of the ongoing research on the interplay between ion channels and changes in the physiology of the nervous system, whether due to development, aging or disease.

Within the nervous system, ion channels prototypically mediate synaptic transmission, which cannot be modulated without ultimately changing the function of some of the underlying ion channels. However, the roles played by ion channels in astrocytes and microglia, as well as in glia-neuron and glia-glia interactions are by now well ascertained. The function of ion channels shapes (and is shaped by) events ranging from brain development and learning in healthy conditions to neuroinflammatory states in response to trauma and infection.

We welcome contributions on the many processes in which ion channels are involved, in the central and peripheral nervous system, during maturation, aging or disease. We hope to receive works spanning topics from basic channel function and modulation, to synaptic plasticity, to neuron-glia interactions in  physiological and pathological conditions.

Early Bird Discount:

  • A 10% discount applies for submissions sent before 31 December 2021.
  • The APC remains at 1600 CHF for submissions sent in early 2022 (before 28 February 2022).

Dr. Francesca Grassi
Dr. Maria Amalia Di Castro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ion channels
  • central nervous system
  • neurons
  • astrocytes
  • microglia
  • synapses
  • synaptic transmission
  • channelopathy
  • neuroinflammation
  • development
  • aging

Published Papers (4 papers)

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Research

11 pages, 839 KiB  
Article
GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol
by Gabriele Ruffolo, Alessandro Gaeta, Beatrice Cannata, Camilla Pinzaglia, Eleonora Aronica, Alessandra Morano, Pierangelo Cifelli and Eleonora Palma
Life 2022, 12(12), 2042; https://doi.org/10.3390/life12122042 - 6 Dec 2022
Cited by 8 | Viewed by 1932
Abstract
Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has [...] Read more.
Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has been approved for treatment as an add-on therapy in patients afflicted by severe pharmaco-resistant epilepsy, including Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS) and tuberous sclerosis complex (TSC). CBD is pharmacologically considered a “dirty drug”, since it has the capacity to bind different targets and to activate several cellular pathways. GABAergic impairment is one of the key processes during the epileptogenesis period able to induce a generalized hyperexcitability of the central nervous system (CNS), leading to epileptic seizures. Here, by using the microtransplantation of human brain membranes approach in Xenopus oocytes and electrophysiological recordings, we confirm the ability of CBD to modulate GABAergic neurotransmission in human cerebral tissues obtained from patients afflicted by different forms of pharmaco-resistant epilepsies, such as DS, TSC, focal cortical dysplasia (FCD) type IIb and temporal lobe epilepsy (TLE). Furthermore, using cDNAs encoding for human GABAA receptor subunits, we found that α1β2 receptors are still affected by CBD, while classical benzodiazepine lost its efficacy as expected. Full article
(This article belongs to the Special Issue Ion Channels and Synaptic Transmission in the Differrent Phases of Life)
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17 pages, 2358 KiB  
Article
Human iPSC-Derived Cortical Neurons Display Homeostatic Plasticity
by Federica Cordella, Laura Ferrucci, Chiara D’Antoni, Silvia Ghirga, Carlo Brighi, Alessandro Soloperto, Ylenia Gigante, Davide Ragozzino, Paola Bezzi and Silvia Di Angelantonio
Life 2022, 12(11), 1884; https://doi.org/10.3390/life12111884 - 14 Nov 2022
Cited by 4 | Viewed by 3595
Abstract
Maintaining the excitability of neurons and circuits is fundamental for healthy brain functions. The global compensatory increase in excitatory synaptic strength, in response to decreased activity, is one of the main homeostatic mechanisms responsible for such regulation. This type of plasticity has been [...] Read more.
Maintaining the excitability of neurons and circuits is fundamental for healthy brain functions. The global compensatory increase in excitatory synaptic strength, in response to decreased activity, is one of the main homeostatic mechanisms responsible for such regulation. This type of plasticity has been extensively characterized in rodents in vivo and in vitro, but few data exist on human neurons maturation. We have generated an in vitro cortical model system, based on differentiated human-induced pluripotent stem cells, chronically treated with tetrodotoxin, to investigate homeostatic plasticity at different developmental stages. Our findings highlight the presence of homeostatic plasticity in human cortical networks and show that the changes in synaptic strength are due to both pre- and post-synaptic mechanisms. Pre-synaptic plasticity involves the potentiation of neurotransmitter release machinery, associated to an increase in synaptic vesicle proteins expression. At the post-synaptic level, we report an increase in the expression of post-synaptic density proteins, involved in glutamatergic receptor anchoring. These results extend our understanding of neuronal homeostasis and reveal the developmental regulation of its expression in human cortical networks. Since induced pluripotent stem cell-derived neurons can be obtained from patients with neurodevelopmental and neurodegenerative diseases, our platform offers a versatile model for assessing human neural plasticity under physiological and pathological conditions. Full article
(This article belongs to the Special Issue Ion Channels and Synaptic Transmission in the Differrent Phases of Life)
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12 pages, 2055 KiB  
Article
Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse
by Marta Morotti, Alessandro Gaeta, Cristina Limatola, Myriam Catalano, Maria Amalia Di Castro and Francesca Grassi
Life 2022, 12(11), 1861; https://doi.org/10.3390/life12111861 - 12 Nov 2022
Viewed by 1188
Abstract
Dystrophin is a cytoskeletal protein contributing to the organization of the neuromuscular junction. In Duchenne muscular dystrophy, due to dystrophin absence, the distribution of endplate acetylcholine receptors (AChRs) becomes disorganized. It is still debated whether this is due to the absence of dystrophin [...] Read more.
Dystrophin is a cytoskeletal protein contributing to the organization of the neuromuscular junction. In Duchenne muscular dystrophy, due to dystrophin absence, the distribution of endplate acetylcholine receptors (AChRs) becomes disorganized. It is still debated whether this is due to the absence of dystrophin or to the repeated damage/regeneration cycles typical of dystrophic muscle. We addressed this controversy studying the endplate in the first 3 postnatal weeks, when muscle damage in dystrophic (mdx) mice is minimal. By synaptic and extra-synaptic patch-clamp recordings in acutely dissociated mdx and wt muscle fibers, we recorded unitary events due to openings of AChR-channels containing the γ and ε subunit. We also examined AChR distribution at the endplate by immunofluorescence assays. No differences between wt and mdx fibers were found in the γ/ε switch, nor in the AChR organization at the endplates up to 21 postnatal days. Conversely, we detected a delayed appearance and disappearance of patches with high channel opening frequency in mdx fibers. Our data emphasize that the innervation-dependent γ/ε switch and AChR organization in the endplate are not affected by the absence of dystrophin, while extra-synaptic AChR cluster formation and disassembly could be differentially regulated in mdx mice. Full article
(This article belongs to the Special Issue Ion Channels and Synaptic Transmission in the Differrent Phases of Life)
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14 pages, 7442 KiB  
Article
5-HT3 Receptors in Rat Dorsal Root Ganglion Neurons: Ca2+ Entry and Modulation of Neurotransmitter Release
by Katiuscia Martinello, Antonietta Sucapane and Sergio Fucile
Life 2022, 12(8), 1178; https://doi.org/10.3390/life12081178 - 2 Aug 2022
Cited by 3 | Viewed by 1382
Abstract
Rat dorsal root ganglion (DRG) neurons express 5-hydroxytryptamine receptors (5-HT3Rs). To elucidate their physiological role in the modulation of sensory signaling, we aimed to quantify their functional expression in newborn and adult rat DRG neurons, as well as their ability to modulate the [...] Read more.
Rat dorsal root ganglion (DRG) neurons express 5-hydroxytryptamine receptors (5-HT3Rs). To elucidate their physiological role in the modulation of sensory signaling, we aimed to quantify their functional expression in newborn and adult rat DRG neurons, as well as their ability to modulate the Ca2+-dependent neurotransmitter release, by means of electrophysiological techniques combined with fluorescence-based Ca2+ imaging. The selective 5-HT3R agonist mCPBG (10 μM) elicited whole-cell currents in 92.5% of adult DRG neurons with a significantly higher density current than in responding newborn cells (52.2%), suggesting an increasing serotoninergic modulation on primary afferent cells during development. Briefly, 5-HT3Rs expressed by adult DRG neurons are permeable to Ca2+ ions, with a measured fractional Ca2+ current (i.e., the percentage of total current carried by Ca2+ ions, Pf) of 1.0%, similar to the value measured for the human heteromeric 5-HT3A/B receptor (Pf = 1.1%), but lower than that of the human homomeric 5-HT3A receptor (Pf = 3.5%). mCPBG applied to co-cultures of newborn DRG and spinal neurons significantly increased the miniature excitatory postsynaptic currents (mEPSCs) frequency in a subset of recorded spinal neurons, even in the presence of Cd2+, a voltage-activated Ca2+ channel blocker. Considered together, our findings indicate that the Ca2+ influx through heteromeric 5-HT3Rs is sufficient to increase the spontaneous neurotransmitter release from DRG to spinal neurons. Full article
(This article belongs to the Special Issue Ion Channels and Synaptic Transmission in the Differrent Phases of Life)
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