Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Ion Conductance and Ion Regulation in Human Health and Disease

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 7718

Share This Special Issue

Special Issue Editor

Prof. Dr. Lars Kaestner

E-Mail Website
Guest Editor

Theoretical Medicine and Biosciences, Saarland University, Saarbruecken, Germany
Interests: red blood cells; ion channels; calcium signaling; microscopy; hematology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gradients in ion concentration across the cell membrane are associated with many processes that define life. Therefore, the knowledge of ion conductance and ion regulation is vital to understanding cellular physiology and pathophysiology. This Special Issue deals with structures and functions of ion transport across membranes, with ion regulation based on intracellular ion stores and signaling processes involving ion transport. It includes studies of excitable cells but also covers non-excitable cells. Studies on model cells and cell lines as well as primary cells and tissue are welcome. This Special Issue covers original research and comprehensive reviews.

Since IJMS is a journal of molecular science, pure clinical studies will not be suitable for this Special Issue; however, clinical submissions with biomolecular experiments are welcome.

Prof. Dr. Lars Kaestner
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 channels
membrane potential
action potential
ion pumps
uniporter
co-transporter
patch-clamp
ion flux
concentration gradient
ion stores

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

13 pages, 3791 KiB

Open AccessArticle

Functional Interdependence of Anoctamins May Influence Conclusions from Overexpression Studies

by Jiraporn Ousingsawat, Rainer Schreiber and Karl Kunzelmann

Int. J. Mol. Sci. 2024, 25(18), 9998; https://doi.org/10.3390/ijms25189998 - 17 Sep 2024

Viewed by 625

Abstract

Anoctamin 6 (ANO6, TMEM16F) is a phospholipid (PL) scramblase that moves PLs between both plasma membrane (PM) leaflets and operates as an ion channel. It plays a role in development and is essential for hemostasis, bone mineralization and immune defense. However, ANO6 has also been shown to regulate cellular Ca²⁺ signaling and PM compartments, thereby controlling the expression of ion channels such as CFTR. Given these pleiotropic effects, we investigated the functional interdependence of the ubiquitous ANO6 with other commonly co-expressed anoctamins. As most expression studies on anoctamins use HEK293 human embryonic kidney cells, we compared ion currents, PL scrambling and Ca²⁺ signals induced by the overexpression of anoctamins in HEK293 wild-type parental and ANO6-knockout cells. The data suggest that the endogenous expression of ANO6 significantly affects the results obtained from overexpressed anoctamins, particularly after increasing intracellular Ca²⁺. Thus, a significant interdependence of anoctamins may influence the interpretation of data obtained from the functional analysis of overexpressed anoctamins. Full article

(This article belongs to the Special Issue Ion Conductance and Ion Regulation in Human Health and Disease)

► Show Figures

Figure 1

19 pages, 3625 KiB

Open AccessArticle

Investigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca²⁺-Dependent Activation of the Calcium-Gated Potassium SK4 Channel

by Émilie Segura, Juan Zhao, Marlena Broszczak, Frédéric Audet, Rémy Sauvé and Lucie Parent

Int. J. Mol. Sci. 2024, 25(8), 4255; https://doi.org/10.3390/ijms25084255 - 11 Apr 2024

Viewed by 1305

Abstract

Ca²⁺ binding to the ubiquitous Ca²⁺ sensing protein calmodulin (CaM) activates the intermediate conductance Ca²⁺-activated SK4 channel. Potential hydrophilic pockets for CaM binding have been identified at the intracellular HA and HB helices in the C-terminal of SK4 from the three published cryo-EM structures of SK4. Single charge reversal substitutions at either site, significantly weakened the pull-down of SK4 by CaM wild-type (CaM), and decreased the TRAM-34 sensitive outward K⁺ current densities in native HEK293T cells when compared with SK4 WT measured under the same conditions. Only the doubly substituted SK4 R352D/R355D (HB helix) obliterated the CaM-mediated pull-down and thwarted outward K⁺ currents. However, overexpression of CaM E84K/E87K, which had been predicted to face the arginine doublet, restored the CaM-mediated pull-down of SK4 R352D/R355D and normalized its whole-cell current density. Virtual analysis of the putative salt bridges supports a unique role for the positively charged arginine doublet at the HB helix into anchoring the interaction with the negatively charged CaM glutamate 84 and 87 CaM. Our findings underscore the unique contribution of electrostatic interactions in carrying CaM binding onto SK4 and support the role of the C-terminal HB helix to the Ca²⁺-dependent gating process. Full article

(This article belongs to the Special Issue Ion Conductance and Ion Regulation in Human Health and Disease)

► Show Figures

Figure 1

20 pages, 2783 KiB

Open AccessArticle

MLe-KCNQ2: An Artificial Intelligence Model for the Prognosis of Missense KCNQ2 Gene Variants

by Alba Saez-Matia, Markel G. Ibarluzea, Sara M-Alicante, Arantza Muguruza-Montero, Eider Nuñez, Rafael Ramis, Oscar R. Ballesteros, Diego Lasa-Goicuria, Carmen Fons, Mónica Gallego, Oscar Casis, Aritz Leonardo, Aitor Bergara and Alvaro Villarroel

Int. J. Mol. Sci. 2024, 25(5), 2910; https://doi.org/10.3390/ijms25052910 - 2 Mar 2024

Cited by 1 | Viewed by 1782

Abstract

Despite the increasing availability of genomic data and enhanced data analysis procedures, predicting the severity of associated diseases remains elusive in the absence of clinical descriptors. To address this challenge, we have focused on the K_V7.2 voltage-gated potassium channel gene (KCNQ2), known for its link to developmental delays and various epilepsies, including self-limited benign familial neonatal epilepsy and epileptic encephalopathy. Genome-wide tools often exhibit a tendency to overestimate deleterious mutations, frequently overlooking tolerated variants, and lack the capacity to discriminate variant severity. This study introduces a novel approach by evaluating multiple machine learning (ML) protocols and descriptors. The combination of genomic information with a novel Variant Frequency Index (VFI) builds a robust foundation for constructing reliable gene-specific ML models. The ensemble model, MLe-KCNQ2, formed through logistic regression, support vector machine, random forest and gradient boosting algorithms, achieves specificity and sensitivity values surpassing 0.95 (AUC-ROC > 0.98). The ensemble MLe-KCNQ2 model also categorizes pathogenic mutations as benign or severe, with an area under the receiver operating characteristic curve (AUC-ROC) above 0.67. This study not only presents a transferable methodology for accurately classifying KCNQ2 missense variants, but also provides valuable insights for clinical counseling and aids in the determination of variant severity. The research context emphasizes the necessity of precise variant classification, especially for genes like KCNQ2, contributing to the broader understanding of gene-specific challenges in the field of genomic research. The MLe-KCNQ2 model stands as a promising tool for enhancing clinical decision making and prognosis in the realm of KCNQ2-related pathologies. Full article

(This article belongs to the Special Issue Ion Conductance and Ion Regulation in Human Health and Disease)

► Show Figures

Figure 1

8 pages, 1058 KiB

Open AccessCommunication

Activity of Potassium Channels in CD8⁺ T Lymphocytes: Diagnostic and Prognostic Biomarker in Ovarian Cancer?

by Vivien Jusztus, Ghofrane Medyouni, Adrienn Bagosi, Rudolf Lampé, György Panyi, Orsolya Matolay, Eszter Maka, Zoárd Tibor Krasznai, Orsolya Vörös and Péter Hajdu

Int. J. Mol. Sci. 2024, 25(4), 1949; https://doi.org/10.3390/ijms25041949 - 6 Feb 2024

Viewed by 1455

Abstract

CD8⁺ T cells play a role in the suppression of tumor growth and immunotherapy. Ion channels control the Ca²⁺-dependent function of CD8⁺ lymphocytes such as cytokine/granzyme production and tumor killing. Kv1.3 and KCa3.1 K⁺ channels stabilize the negative membrane potential of T cells to maintain Ca²⁺ influx through CRAC channels. We assessed the expression of Kv1.3, KCa3.1 and CRAC in CD8⁺ cells from ovarian cancer (OC) patients (n = 7). We found that the expression level of Kv1.3 was higher in patients with malignant tumors than in control or benign tumor groups while the KCa3.1 activity was lower in the malignant tumor group as compared to the others. We demonstrated that the Ca²⁺ response in malignant tumor patients is higher compared to control groups. We propose that altered Kv1.3 and KCa3.1 expression in CD8⁺ cells in OC could be a reporter and may serve as a biomarker in diagnostics and that increased Ca²⁺ response through CRAC may contribute to the impaired CD8⁺ function. Full article

(This article belongs to the Special Issue Ion Conductance and Ion Regulation in Human Health and Disease)

► Show Figures

Figure 1

24 pages, 4246 KiB

Open AccessArticle

The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells

by Polina Petkova-Kirova, Nicoletta Murciano, Giulia Iacono, Julia Jansen, Greta Simionato, Min Qiao, Carmen van der Zwaan, Maria Giustina Rotordam, Thomas John, Laura Hertz, Arjan J. Hoogendijk, Nadine Becker, Christian Wagner, Marieke von Lindern, Stephane Egee, Emile van den Akker and Lars Kaestner

Int. J. Mol. Sci. 2024, 25(3), 1416; https://doi.org/10.3390/ijms25031416 - 24 Jan 2024

Cited by 1 | Viewed by 1846

Abstract

The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties. Both the Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single-digit range, can be detected through transcriptome analysis of reticulocytes. Proteomics analysis of reticulocytes and mature RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch clamp method. While for the Gárdos channel, the activity in terms of ion currents is higher in reticulocytes compared to mature RBCs, for Piezo1, the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs. We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis. Full article

(This article belongs to the Special Issue Ion Conductance and Ion Regulation in Human Health and Disease)

► Show Figures

Journal Menu

Journal Browser

Ion Conductance and Ion Regulation in Human Health and Disease

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (5 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI