Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.3
5.5
Journals
Biomolecules
Special Issues
Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology...
share announcement

Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11205

Special Issue Editors

Dr. Tiandong Leng

E-Mail
Guest Editor
Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, USA
Interests: ion channel; TRP; NMDAR; VGSC; neuroprotection; stroke; glioma
Prof. Dr. Zhigang Xiong

E-Mail
Guest Editor
Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, USA
Interests: ischemic stroke; Alzheimer’s disease; TRPM7; ASIC
Dr. Baoming Wu

E-Mail Website
Guest Editor
School of Pharmacy, Anhui Medical University, Hefei, China
Interests: potassium channel; inflammation; cell injury; liver diseases; cancer
Dr. Xinbo Li

E-Mail
Guest Editor
Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239, USA
Interests: connexin 36; electrical synapses; tight junctions; gap junctions; connexins; PDZ domains; Rodentia; oligodendroglia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ion channels are transmembrane proteins composed of several subunits that form gated aqueous pores for the movement of ions across cell membranes. They selectively conduct specific ions and play key roles in electrical signalling. Ion channels are gated by a multitude of signals, including membrane potential, chemical agents (ligands), mechanical stimuli, temperature, or a combination of such signals. Moreover, ion channel activities are often modified by exogenous substances such as poisons, toxins, and drugs. A large number of ion channel genes exist that confer a wide range of functional characteristics, thus allowing different types of cells that express different types of ion channels to have a remarkable spectrum of electrical properties. Ion channels play important roles in such diverse processes as nerve excitability and muscle excitation, hormonal secretion, cell proliferation, sensory transduction, and high-order cerebral functions such as learning and memory. Not surprisingly, the malfunction of ion channels has been found to be associated with a wide variety of diseases including epilepsy, stroke, pain, cystic fibrosis, skeletal muscle disorders, certain types of cardiac arrhythmias, and many others. Understanding the genetics, molecular structure, biophysical properties, gating and regulatory mechanisms will provide a basic understanding of this exceptional ion channel diversity. Moreover, an investigation of their role in physiology and disease will also provide additional insight into ion channel function, which may ultimately lead to the identification of novel targets for disease treatment.

The aim of this Special Issue is to provide an informative and up-to-date understanding of the structure, function, regulatory mechanisms, and physiological and pathophysiological roles of the various ion channels that are expressed in different cell types or organs.

We welcome original research articles and reviews, including, but not limited to, the following themes:

  • Biophysical, biochemical, and molecular biological studies of the structure of ion channels, and the structure–function relationship.
  • The modulation of ion channels by endogenous molecules, including intracellular and extracellular and exogenous substances, including naturally occurring or synthetic compounds.
  • Mutations of ion channel genes that lead to the gain or loss of functions.
  • Diseases resulting from the defective regulation of channels by cellular constituents or extracellular ligands.

Dr. Tiandong Leng
Prof. Dr. Zhigang Xiong
Dr. Baoming Wu
Dr. Xinbo Li
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. Biomolecules 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 2700 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
  • voltage-gated channels
  • ligand-gated channels
  • gap-junction channels
  • channelopathy

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 3401 KiB  
Article
Inhibition of Acid-Sensing Ion Channels by KB-R7943, a Reverse Na+/Ca2+ Exchanger Inhibitor
by Hua-Wei Sun, Xiang-Ping Chu, Roger P. Simon, Zhi-Gang Xiong and Tian-Dong Leng
Biomolecules 2023, 13(3), 507; https://doi.org/10.3390/biom13030507 - 10 Mar 2023
Cited by 1 | Viewed by 1321
Abstract
KB-R7943, an isothiourea derivative, is widely used as a pharmacological inhibitor of reverse sodium–calcium exchanger (NCX). It has been shown to have neuroprotective and analgesic effects in animal models; however, the detailed molecular mechanisms remain elusive. In the current study, we investigated whether [...] Read more.
KB-R7943, an isothiourea derivative, is widely used as a pharmacological inhibitor of reverse sodium–calcium exchanger (NCX). It has been shown to have neuroprotective and analgesic effects in animal models; however, the detailed molecular mechanisms remain elusive. In the current study, we investigated whether KB-R7943 modulates acid-sensing ion channels (ASICs), a group of proton-gated cation channels implicated in the pathophysiology of various neurological disorders, using the whole-cell patch clamp techniques. Our data show that KB-R7943 irreversibly inhibits homomeric ASIC1a channels heterologously expressed in Chinese Hamster Ovary (CHO) cells in a use- and concentration-dependent manner. It also reversibly inhibits homomeric ASIC2a and ASIC3 channels in CHO cells. Both the transient and sustained current components of ASIC3 are inhibited. Furthermore, KB-R7943 inhibits ASICs in primary cultured peripheral and central neurons. It inhibits the ASIC-like currents in mouse dorsal root ganglion (DRG) neurons and the ASIC1a-like currents in mouse cortical neurons. The inhibition of the ASIC1a-like current is use-dependent and unrelated to its effect on NCX since neither of the other two well-characterized NCX inhibitors, including SEA0400 and SN-6, shows an effect on ASIC. Our data also suggest that the isothiourea group, which is lacking in other structurally related analogs that do not affect ASIC1a-like current, may serve as a critical functional group. In summary, we characterize KB-R7943 as a new ASIC inhibitor. It provides a novel pharmacological tool for the investigation of the functions of ASICs and could serve as a lead compound for developing small-molecule drugs for treating ASIC-related disorders. Full article
(This article belongs to the Special Issue Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology and Disease)
►▼ Show Figures

Figure 1

15 pages, 18340 KiB  
Article
Changes in NMDA Receptor Function in Rapid Ischemic Tolerance: A Potential Role for Tri-Heteromeric NMDA Receptors
by Mian Xie, Tiandong Leng, Samaneh Maysami, Andrea Pearson, Roger Simon, Zhi-Gang Xiong and Robert Meller
Biomolecules 2022, 12(9), 1214; https://doi.org/10.3390/biom12091214 - 01 Sep 2022
Cited by 1 | Viewed by 1671
Abstract
In this study, we characterize biophysical changes in NMDA receptor function in response to brief non-injurious ischemic stress (ischemic preconditioning). Electrophysiological studies show NMDA receptor function is reduced following preconditioning in cultured rat cortical neurons. This functional change is not due to changes [...] Read more.
In this study, we characterize biophysical changes in NMDA receptor function in response to brief non-injurious ischemic stress (ischemic preconditioning). Electrophysiological studies show NMDA receptor function is reduced following preconditioning in cultured rat cortical neurons. This functional change is not due to changes in the reversal potential of the receptor, but an increase in desensitization. We performed concentration–response analysis of NMDA-evoked currents, and demonstrate that preconditioned neurons show a reduced potency of NMDA to evoke currents, an increase in Mg2+ sensitivity, but no change in glycine sensitivity. Antagonists studies show a reduced inhibition of GluN2B antagonists that have an allosteric mode of action (ifenprodil and R-25-6981), but competitive antagonists at the GluR2A and 2B receptor (NVP-AMM077 and conantokin-G) appear to have similar potency to block currents. Biochemical studies show a reduction in membrane surface GluN2B subunits, and an increased co-immunoprecipitation of GluN2A with GluN2B subunits, suggestive of tri-heteromeric receptor formation. Finally, we show that blocking actin remodeling with jasplakinolide, a mechanism of rapid ischemic tolerance, prevents NMDA receptor functional changes and co-immunoprecipitation of GluN2A and 2B subunits. Together, this study shows that alterations in NMDA receptor function following preconditioning ischemia are associated with neuroprotection in rapid ischemic tolerance. Full article
(This article belongs to the Special Issue Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology and Disease)
►▼ Show Figures

Figure 1

Review

Jump to: Research

0 pages, 11412 KiB  
Review
The Structural–Functional Crosstalk of the Calsequestrin System: Insights and Pathological Implications
by Chiara Marabelli, Demetrio J. Santiago and Silvia G. Priori
Biomolecules 2023, 13(12), 1693; https://doi.org/10.3390/biom13121693 - 23 Nov 2023
Viewed by 2770
Abstract
Calsequestrin (CASQ) is a key intra-sarcoplasmic reticulum Ca2+-handling protein that plays a pivotal role in the contraction of cardiac and skeletal muscles. Its Ca2+-dependent polymerization dynamics shape the translation of electric excitation signals to the Ca2+-induced contraction [...] Read more.
Calsequestrin (CASQ) is a key intra-sarcoplasmic reticulum Ca2+-handling protein that plays a pivotal role in the contraction of cardiac and skeletal muscles. Its Ca2+-dependent polymerization dynamics shape the translation of electric excitation signals to the Ca2+-induced contraction of the actin-myosin architecture. Mutations in CASQ are linked to life-threatening pathological conditions, including tubular aggregate myopathy, malignant hyperthermia, and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The variability in the penetrance of these phenotypes and the lack of a clear understanding of the disease mechanisms associated with CASQ mutations pose a major challenge to the development of effective therapeutic strategies. In vitro studies have mainly focused on the polymerization and Ca2+-buffering properties of CASQ but have provided little insight into the complex interplay of structural and functional changes that underlie disease. In this review, the biochemical and structural natures of CASQ are explored in-depth, while emphasizing their direct and indirect consequences for muscle Ca2+ physiology. We propose a novel functional classification of CASQ pathological missense mutations based on the structural stability of the monomer, dimer, or linear polymer conformation. We also highlight emerging similarities between polymeric CASQ and polyelectrolyte systems, emphasizing the potential for the use of this paradigm to guide further research. Full article
(This article belongs to the Special Issue Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology and Disease)
►▼ Show Figures

Figure 1

14 pages, 1225 KiB  
Review
Regulation of Epithelial Sodium Transport by SARS-CoV-2 Is Closely Related with Fibrinolytic System-Associated Proteins
by Tingyu Wang, Yiman Zhai, Hao Xue, Wei Zhou, Yan Ding and Hongguang Nie
Biomolecules 2023, 13(4), 578; https://doi.org/10.3390/biom13040578 - 23 Mar 2023
Cited by 1 | Viewed by 2045
Abstract
Dyspnea and progressive hypoxemia are the main clinical features of patients with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary pathology shows diffuse alveolar damage with edema, hemorrhage, and the deposition of fibrinogens in the [...] Read more.
Dyspnea and progressive hypoxemia are the main clinical features of patients with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary pathology shows diffuse alveolar damage with edema, hemorrhage, and the deposition of fibrinogens in the alveolar space, which are consistent with the Berlin Acute Respiratory Distress Syndrome Criteria. The epithelial sodium channel (ENaC) is a key channel protein in alveolar ion transport and the rate-limiting step for pulmonary edema fluid clearance, the dysregulation of which is associated with acute lung injury/acute respiratory distress syndrome. The main protein of the fibrinolysis system, plasmin, can bind to the furin site of γ-ENaC and induce it to an activation state, facilitating pulmonary fluid reabsorption. Intriguingly, the unique feature of SARS-CoV-2 from other β-coronaviruses is that the spike protein of the former has the same furin site (RRAR) with ENaC, suggesting that a potential competition exists between SARS-CoV-2 and ENaC for the cleavage by plasmin. Extensive pulmonary microthrombosis caused by disorders of the coagulation and fibrinolysis system has also been seen in COVID-19 patients. To some extent, high plasmin (ogen) is a common risk factor for SARS-CoV-2 infection since an increased cleavage by plasmin accelerates virus invasion. This review elaborates on the closely related relationship between SARS-CoV-2 and ENaC for fibrinolysis system-related proteins, aiming to clarify the regulation of ENaC under SARS-CoV-2 infection and provide a novel reference for the treatment of COVID-19 from the view of sodium transport regulation in the lung epithelium. Full article
(This article belongs to the Special Issue Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology and Disease)
►▼ Show Figures

Figure 1

27 pages, 1671 KiB  
Review
Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities
by Hong-Yu Liang, Huan-Xin Yin, Shu-Fang Li, Yong Chen, Ying-Jie Zhao, Wei Hu and Ren-Peng Zhou
Biomolecules 2022, 12(10), 1383; https://doi.org/10.3390/biom12101383 - 27 Sep 2022
Cited by 5 | Viewed by 2553
Abstract
Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies–autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients’ [...] Read more.
Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies–autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients’ quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellular activities and the body has evolved a rigorous calcium signaling system. Calcium-permeable channels, as the main operators of calcium signaling, are widely distributed in cell membranes, endoplasmic reticulum membranes and mitochondrial membranes, and mediate the efflux and entry of Ca2+. Over the last century, more and more calcium-permeable channels have been identified in human cells, and the role of this large family of calcium-permeable channels in rheumatoid arthritis has gradually become clear. In this review, we briefly introduce the major calcium-permeable channels involved in the pathogenesis of RA (e.g., acid-sensitive ion channel (ASIC), transient receptor potential (TRP) channel and P2X receptor) and explain the specific roles and mechanisms of these calcium-permeable channels in the pathogenesis of RA, providing more comprehensive ideas and targets for the treatment of RA. Full article
(This article belongs to the Special Issue Ion Channels: Structure, Function, Regulatory Mechanisms and Roles in Physiology and Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop