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Membranes
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Ion Channels on (Bio)Membranes
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Ion Channels on (Bio)Membranes

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Composition and Structures".

Deadline for manuscript submissions: closed (15 January 2022) | Viewed by 16068

Special Issue Editors

Dr. Tadashi Kimura

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Guest Editor
Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
Interests: bioactive peptides; ion channels; venom; tarantula; peptide display; membrane protein
Prof. Dr. Anna Weronika Sobańska

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Co-Guest Editor
Department of Analytical Chemistry, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
Interests: pharmacology; environmental toxicology; liquid chromatography; drug-protein interactions; in silico studies; biological activity of plants; analysis of pharmaceutical and cosmetic preparations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague, 

The cell is the smallest unit of life and is separated from the outside world by the cell membrane to carry out biological activities. The plasma membrane contains a large number of integral membrane proteins that act as ion channels, transporters, and receptors to exchange materials and information with the environment. Ion channels are the fastest signaling pathway in excitatory cells such as neurons. Ion channels respond rapidly to changes in the cell’s environment and are activated by changes in ligands, membrane potential, temperature, tension, and pH. More recently, ion channels have been shown to be essential for such phenomena as secretion, gene expression, and cell division in non-excitable cells. Many diseases have come to be regarded as channel diseases, and research of ion channels is becoming more and more important for the elucidation of the disease state and the development of the therapy. Recently, the development of drugs and pest control drugs using ion channels as target molecules has been advanced, and ion channel research has shown wide development from basic research to applied research. This Special Issue accepts contributions from a wide range of fields, including physiology, pathology, pharmacology, structural biology, and embryology.

Dr. Tadashi Kimura
Dr. Anna Weronika Sobańska
Guest Editor

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. Membranes 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 2200 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 channel physiology
  • Electrophysiology
  • Channelopathy
  • Development
  • Pharmacology
  • Venom
  • Structure–activity relationship
  • Drug discovery

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Published Papers (4 papers)

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Research

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13 pages, 2437 KiB  
Article
Nebivolol as a Potent TRPM8 Channel Blocker: A Drug-Screening Approach through Automated Patch Clamping and Ligand-Based Virtual Screening
by Farhad Jahanfar, Laura Sadofsky, Alyn Morice and Massimo D’Amico
Membranes 2022, 12(10), 954; https://doi.org/10.3390/membranes12100954 - 28 Sep 2022
Cited by 6 | Viewed by 3207
Abstract
Transient Receptor Potential Melastatin 8 (TRPM8) from the melastatin TRP channel subfamily is a non-selective Ca2+-permeable ion channel with multimodal gating which can be activated by low temperatures and cooling compounds, such as menthol and icilin. Different conditions such as neuropathic [...] Read more.
Transient Receptor Potential Melastatin 8 (TRPM8) from the melastatin TRP channel subfamily is a non-selective Ca2+-permeable ion channel with multimodal gating which can be activated by low temperatures and cooling compounds, such as menthol and icilin. Different conditions such as neuropathic pain, cancer, overactive bladder syndrome, migraine, and chronic cough have been linked to the TRPM8 mode of action. Despite the several potent natural and synthetic inhibitors of TRPM8 that have been identified, none of them have been approved for clinical use. The aim of this study was to discover novel blocking TRPM8 agents using automated patch clamp electrophysiology combined with a ligand-based virtual screening based on the SwissSimilarity platform. Among the compounds we have tested, nebivolol and carvedilol exhibited the greatest inhibitory effect, with an IC50 of 0.97 ± 0.15 µM and 9.1 ± 0.6 µM, respectively. This study therefore provides possible candidates for future drug repurposing and suggests promising lead compounds for further optimization as inhibitors of the TRPM8 ion channel. Full article
(This article belongs to the Special Issue Ion Channels on (Bio)Membranes)
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19 pages, 3026 KiB  
Article
TRPV4 Stimulation Level Regulates Ca2+-Dependent Control of Human Corneal Endothelial Cell Viability and Survival
by Jennifer Donau, Huan Luo, Iiris Virta, Annett Skupin, Margarita Pushina, Jana Loeffler, Frauke V. Haertel, Anupam Das, Thomas Kurth, Michael Gerlach, Dirk Lindemann, Peter S. Reinach, Stefan Mergler and Monika Valtink
Membranes 2022, 12(3), 281; https://doi.org/10.3390/membranes12030281 - 28 Feb 2022
Cited by 4 | Viewed by 3036
Abstract
The functional contribution of transient receptor potential vanilloid 4 (TRPV4) expression in maintaining human corneal endothelial cells (HCEC) homeostasis is unclear. Accordingly, we determined the effects of TRPV4 gene and protein overexpression on responses modulating the viability and survival of HCEC. Q-PCR, Western [...] Read more.
The functional contribution of transient receptor potential vanilloid 4 (TRPV4) expression in maintaining human corneal endothelial cells (HCEC) homeostasis is unclear. Accordingly, we determined the effects of TRPV4 gene and protein overexpression on responses modulating the viability and survival of HCEC. Q-PCR, Western blot, FACS analyses and fluorescence single-cell calcium imaging confirmed TRPV4 gene and protein overexpression in lentivirally transduced 12V4 cells derived from their parent HCEC-12 line. Although TRPV4 overexpression did not alter the baseline transendothelial electrical resistance (TEER), its cellular capacitance (Ccl) was larger than that in its parent. Scanning electron microscopy revealed that only the 12V4 cells developed densely packed villus-like protrusions. Stimulation of TRPV4 activity with GSK1016790A (GSK101, 10 µmol/L) induced larger Ca2+ transients in the 12V4 cells than those in the parental HCEC-12. One to ten nmol/L GSK101 decreased 12V4 viability, increased cell death rates and reduced the TEER, whereas 1 µmol/L GSK101 was required to induce similar effects in the HCEC-12. However, the TRPV4 channel blocker RN1734 (1 to 30 µmol/L) failed to alter HCEC-12 and 12V4 morphology, cell viability and metabolic activity. Taken together, TRPV4 overexpression altered both the HCEC morphology and markedly lowered the GSK101 dosages required to stimulate its channel activity. Full article
(This article belongs to the Special Issue Ion Channels on (Bio)Membranes)
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Review

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20 pages, 1771 KiB  
Review
The Role of Chloride Channels in the Multidrug Resistance
by Bartosz Wilczyński, Alicja Dąbrowska, Jolanta Saczko and Julita Kulbacka
Membranes 2022, 12(1), 38; https://doi.org/10.3390/membranes12010038 - 28 Dec 2021
Cited by 10 | Viewed by 2741
Abstract
Nowadays, one of medicine’s main and most challenging aims is finding effective ways to treat cancer. Unfortunately, although there are numerous anti-cancerous drugs, such as cisplatin, more and more cancerous cells create drug resistance. Thus, it is equally important to find new medicines [...] Read more.
Nowadays, one of medicine’s main and most challenging aims is finding effective ways to treat cancer. Unfortunately, although there are numerous anti-cancerous drugs, such as cisplatin, more and more cancerous cells create drug resistance. Thus, it is equally important to find new medicines and research the drug resistance phenomenon and possibilities to avoid this mechanism. Ion channels, including chloride channels, play an important role in the drug resistance phenomenon. Our article focuses on the chloride channels, especially the volume-regulated channels (VRAC) and CLC chloride channels family. VRAC induces multidrug resistance (MDR) by causing apoptosis connected with apoptotic volume decrease (AVD) and VRAC are responsible for the transport of anti-cancerous drugs such as cisplatin. VRACs are a group of heterogenic complexes made from leucine-rich repetition with 8A (LRRC8A) and a subunit LRRC8B-E responsible for the properties. There are probably other subunits, which can create those channels, for example, TTYH1 and TTYH2. It is also known that the ClC family is involved in creating MDR in mainly two mechanisms—by changing the cell metabolism or acidification of the cell. The most researched chloride channel from this family is the CLC-3 channel. However, other channels are playing an important role in inducing MDR as well. In this paper, we review the role of chloride channels in MDR and establish the role of the channels in the MDR phenomenon. Full article
(This article belongs to the Special Issue Ion Channels on (Bio)Membranes)
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35 pages, 62390 KiB  
Review
Artificial Intelligence, Machine Learning and Deep Learning in Ion Channel Bioinformatics
by Md. Ashrafuzzaman
Membranes 2021, 11(9), 672; https://doi.org/10.3390/membranes11090672 - 31 Aug 2021
Cited by 15 | Viewed by 6081
Abstract
Ion channels are linked to important cellular processes. For more than half a century, we have been learning various structural and functional aspects of ion channels using biological, physiological, biochemical, and biophysical principles and techniques. In recent days, bioinformaticians and biophysicists having the [...] Read more.
Ion channels are linked to important cellular processes. For more than half a century, we have been learning various structural and functional aspects of ion channels using biological, physiological, biochemical, and biophysical principles and techniques. In recent days, bioinformaticians and biophysicists having the necessary expertise and interests in computer science techniques including versatile algorithms have started covering a multitude of physiological aspects including especially evolution, mutations, and genomics of functional channels and channel subunits. In these focused research areas, the use of artificial intelligence (AI), machine learning (ML), and deep learning (DL) algorithms and associated models have been found very popular. With the help of available articles and information, this review provide an introduction to this novel research trend. Ion channel understanding is usually made considering the structural and functional perspectives, gating mechanisms, transport properties, channel protein mutations, etc. Focused research on ion channels and related findings over many decades accumulated huge data which may be utilized in a specialized scientific manner to fast conclude pinpointed aspects of channels. AI, ML, and DL techniques and models may appear as helping tools. This review aims at explaining the ways we may use the bioinformatics techniques and thus draw a few lines across the avenue to let the ion channel features appear clearer. Full article
(This article belongs to the Special Issue Ion Channels on (Bio)Membranes)
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