Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Recent Advances in Ion Channels and Ion Channelopathies

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 September 2023) | Viewed by 10493

Share This Special Issue

Special Issue Editor

Dr. Deanne H. Hryciw

E-Mail Website
Guest Editor

School of Environment and Sciences, Griffith University, Nathan, QLD 4111, Australia
Interests: endocannabinoid system; development; cell signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ion channels play critical roles in normal cellular function. In addition, perturbations in ion channel function can lead to the development of disease. These ion channelopathies have the capacity to affect various organ systems, including the nervous, cardiovascular, and endocrine systems, with a significant number of ion channelopathies associated with epithelial systems. Ion channels may be present in protein complexes and may control cellular function by intracellular signaling. Ion channels can affect cell function at the cell membrane or within intracellular organelles. The key to the development of therapeutics targeted toward ion channels is a clear understanding of how these proteins modulate cellular function and how dysfunction leads to pathology.

In this Special Issue, original studies on all aspects of ion channels and ion channelopathies are welcome, with a particular emphasis on molecular analyses of ion channels and the mechanism by which perturbations in function can lead to ion channelopathies.

Dr. Deanne H. Hryciw
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
disease
ion channelopathies
signaling
tissues

Published Papers (6 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research

3 pages, 175 KiB

Open AccessEditorial

Special Issue: “Recent Advances in Ion Channels and Ion Channelopathies”

by Deanne H. Hryciw

Int. J. Mol. Sci. 2024, 25(7), 3598; https://doi.org/10.3390/ijms25073598 - 22 Mar 2024

Viewed by 332

Abstract

The aim of this special issue was to showcase recent advanced in understanding ion channel function and dysfunction associated with disease [...] Full article

(This article belongs to the Special Issue Recent Advances in Ion Channels and Ion Channelopathies)

Research

Jump to: Editorial

10 pages, 3243 KiB

Open AccessArticle

Changes in Essential Fatty Acids and Ileal Genes Associated with Metabolizing Enzymes and Fatty Acid Transporters in Rodent Models of Cystic Fibrosis

by Nirajan Shrestha, Nathan Rout-Pitt, Alexandra McCarron, Courtney A. Jackson, Andrew C. Bulmer, Andrew J. McAinch, Martin Donnelley, David W. Parsons and Deanne H. Hryciw

Int. J. Mol. Sci. 2023, 24(8), 7194; https://doi.org/10.3390/ijms24087194 - 13 Apr 2023

Viewed by 1411

Abstract

Cystic fibrosis (CF), the result of mutations in the CF transmembrane conductance regulator (CFTR), causes essential fatty acid deficiency. The aim of this study was to characterize fatty acid handling in two rodent models of CF; one strain which harbors the loss of phenylalanine at position 508 (Phe508del) in CFTR and the other lacks functional CFTR (510X). Fatty acid concentrations were determined using gas chromatography in serum from Phe508del and 510X rats. The relative expression of genes responsible for fatty acid transport and metabolism were quantified using real-time PCR. Ileal tissue morphology was assessed histologically. There was an age-dependent decrease in eicosapentaenoic acid and the linoleic acid:α-linolenic acid ratio, a genotype-dependent decrease in docosapentaenoic acid (n-3) and an increase in the arachidonic acid:docosahexaenoic acid ratio in Phe508del rat serum, which was not observed in 510X rats. In the ileum, Cftr mRNA was increased in Phe508del rats but decreased in 510X rats. Further, Elvol2, Slc27a1, Slc27a2 and Got2 mRNA were increased in Phe508del rats only. As assessed by Sirius Red staining, collagen was increased in Phe508del and 510X ileum. Thus, CF rat models exhibit alterations in the concentration of circulating fatty acids, which may be due to altered transport and metabolism, in addition to fibrosis and microscopic structural changes in the ileum. Full article

(This article belongs to the Special Issue Recent Advances in Ion Channels and Ion Channelopathies)

► Show Figures

Figure 1

14 pages, 3416 KiB

Open AccessArticle

Functional Effects of Epilepsy Associated KCNT1 Mutations Suggest Pathogenesis via Aberrant Inhibitory Neuronal Activity

by Grigori Y. Rychkov, Zeeshan Shaukat, Chiao Xin Lim, Rashid Hussain, Ben J. Roberts, Claudia M. Bonardi, Guido Rubboli, Brandon F. Meaney, Robyn Whitney, Rikke S. Møller, Michael G. Ricos and Leanne M. Dibbens

Int. J. Mol. Sci. 2022, 23(23), 15133; https://doi.org/10.3390/ijms232315133 - 01 Dec 2022

Cited by 2 | Viewed by 2918

Abstract

KCNT1 (K⁺ channel subfamily T member 1) is a sodium-activated potassium channel highly expressed in the nervous system which regulates neuronal excitability by contributing to the resting membrane potential and hyperpolarisation following a train of action potentials. Gain of function mutations in the KCNT1 gene are the cause of neurological disorders associated with different forms of epilepsy. To gain insights into the underlying pathobiology we investigated the functional effects of 9 recently published KCNT1 mutations, 4 previously studied KCNT1 mutations, and one previously unpublished KCNT1 variant of unknown significance. We analysed the properties of KCNT1 potassium currents and attempted to find a correlation between the changes in KCNT1 characteristics due to the mutations and severity of the neurological disorder they cause. KCNT1 mutations identified in patients with epilepsy were introduced into the full length human KCNT1 cDNA using quick-change site-directed mutagenesis protocol. Electrophysiological properties of different KCNT1 constructs were investigated using a heterologous expression system (HEK293T cells) and patch clamping. All mutations studied, except T314A, increased the amplitude of KCNT1 currents, and some mutations shifted the voltage dependence of KCNT1 open probability, increasing the proportion of channels open at the resting membrane potential. The T314A mutation did not affect KCNT1 current amplitude but abolished its voltage dependence. We observed a positive correlation between the severity of the neurological disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance and suppressing the activity of inhibitory neurons. A reduction in action potential firing in inhibitory neurons due to excessively high resting potassium conductance leads to disinhibition of neural circuits, hyperexcitability and seizures. Full article

(This article belongs to the Special Issue Recent Advances in Ion Channels and Ion Channelopathies)

► Show Figures

Figure 1

18 pages, 3464 KiB

Open AccessArticle

Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Na_v1.7 Voltage-Gated Sodium Channel

by Haoyi Yang, Zhiming Shan, Weijie Guo, Yuwei Wang, Shuxian Cai, Fuyi Li, Qiaojie Huang, Jessica Aijia Liu, Chi Wai Cheung and Song Cai

Int. J. Mol. Sci. 2022, 23(23), 14842; https://doi.org/10.3390/ijms232314842 - 27 Nov 2022

Cited by 4 | Viewed by 2486

Abstract

Neuropathic pain is a refractory chronic disease affecting millions of people worldwide. Given that present painkillers have poor efficacy or severe side effects, developing novel analgesics is badly needed. The multiplex structure of active ingredients isolated from natural products provides a new source for phytochemical compound synthesis. Here, we identified a natural product, Narirutin, a flavonoid compound isolated from the Citrus unshiu, showing antinociceptive effects in rodent models of neuropathic pain. Using calcium imaging, whole-cell electrophysiology, western blotting, and immunofluorescence, we uncovered a molecular target for Narirutin’s antinociceptive actions. We found that Narirutin (i) inhibits Veratridine-triggered nociceptor activities in L4-L6 rat dorsal root ganglion (DRG) neurons, (ii) blocks voltage-gated sodium (Na_V) channels subtype 1.7 in both small-diameter DRG nociceptive neurons and human embryonic kidney (HEK) 293 cell line, (iii) does not affect tetrodotoxin-resistant (TTX-R) Na_V channels, and (iv) blunts the upregulation of Na_v1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Na_v1.7 as a molecular target of Narirutin may further clarify the analgesic mechanism of natural flavonoid compounds and provide an optimal idea to produce novel selective and efficient analgesic drugs. Full article

(This article belongs to the Special Issue Recent Advances in Ion Channels and Ion Channelopathies)

► Show Figures

Figure 1

19 pages, 8657 KiB

Open AccessArticle

The α₂δ Calcium Channel Subunit Accessorily and Independently Affects the Biological Function of Ditylenchus destructor

by Xueling Chen, Mingwei An, Shan Ye, Zhuhong Yang and Zhong Ding

Int. J. Mol. Sci. 2022, 23(21), 12999; https://doi.org/10.3390/ijms232112999 - 27 Oct 2022

Cited by 2 | Viewed by 1124

Abstract

The α₂δ subunit is a high-voltage activated (HVA) calcium channel (Ca_v1 and Ca_v2) auxiliary subunit that increases the density and function of HVA calcium channels in the plasma membrane of mammals. However, its function in plant parasitic nematodes remains unknown. In this study, we cloned the full-length cDNA sequence of the voltage-gated calcium channel (VGCC) α₂δ subunit (named DdCa_vα₂δ) in Ditylenchus destructor. We found that DdCa_vα₂δ tends to be expressed in the egg stage, followed by the J3 stage. RNA-DIG in situ hybridization experiments showed that the DdCa_vα₂δ subunit was expressed in the body wall, esophageal gland, uterus, post uterine, and spicules of D. destructor. The in vitro application of RNA interference (RNAi) affected the motility, reproduction, chemotaxis, stylet thrusting, and protein secretion of D. destructor to different degrees by targeting DdCα1D, DdCα1A, and DdCa_vα₂δ in J3 stages, respectively. Based on the results of RNAi experiments, it was hypothesized that L-type VGCC may affect the motility, chemotaxis, and stylet thrusting of D. destructor. Non-L-type VGCC may affect the protein secretion and reproduction of D. destructor. The DdCa_vα₂δ subunit gene also affected the motility, chemotaxis, and reproduction of D. destructor. These findings reveal the independent function of the VGCC α₂δ subunit in D. destructor as well as give a theoretical foundation for future research on plant parasitic nematode VGCC. Full article

(This article belongs to the Special Issue Recent Advances in Ion Channels and Ion Channelopathies)

► Show Figures

Figure 1

15 pages, 4638 KiB

Open AccessArticle

Genetic Variant in Nicotinic Receptor α4-Subunit Causes Sleep-Related Hyperkinetic Epilepsy via Increased Channel Opening

by Simone Mazzaferro, Deborah J. Msekela, Edward C. Cooper, Atul Maheshwari and Steven M. Sine

Int. J. Mol. Sci. 2022, 23(20), 12124; https://doi.org/10.3390/ijms232012124 - 12 Oct 2022

Cited by 4 | Viewed by 1510

Abstract

We describe genetic and molecular-level functional alterations in the α4β2 neuronal nicotinic acetylcholine receptor (nAChR) from a patient with sleep-related hyperkinetic epilepsy and a family history of epilepsy. Genetic sequencing revealed a heterozygous variant c.851C>G in the CHRNA4 gene encoding the α4 subunit, resulting in the missense mutation p.Ser284Trp. Patch clamp recordings from genetically engineered nAChRs incorporating the α4-Ser284Trp subunit revealed aberrant channel openings in the absence of agonist and markedly prolonged openings in its presence. Measurements of single channel current amplitude distinguished two pentameric stoichiometries of the variant nAChR containing either two or three copies of the α4-Ser284Trp subunit, each exhibiting aberrant spontaneous and prolonged agonist-elicited channel openings. The α4-Ser284 residue is highly conserved and located within the M2 transmembrane α-helix that lines the ion channel. When mapped onto the receptor’s three-dimensional structure, the larger Trp substitution sterically clashes with the M2 α-helix from the neighboring subunit, promoting expansion of the pore and stabilizing the open relative to the closed conformation of the channel. Together, the clinical, genetic, functional, and structural observations demonstrate that α4-Ser284Trp enhances channel opening, predicting increased membrane excitability and a pathogenic seizure phenotype. Full article

(This article belongs to the Special Issue Recent Advances in Ion Channels and Ion Channelopathies)

► Show Figures

Journal Menu

Journal Browser

Recent Advances in Ion Channels and Ion Channelopathies

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (6 papers)

Editorial

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI