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Role of Ion Channels in Human Health and Diseases
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Role of Ion Channels in Human Health and Diseases

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: closed (20 December 2025) | Viewed by 4169

Special Issue Editor

Prof. Dr. Sheng-Nan Wu

E-Mail Website
Guest Editor
Department Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Interests: electrophysiology; ionic channel; cellular electrophysiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ion channels are pathways across cell membranes. These channels are highly selective for ion permeability and exhibit different gating kinetics. Changes in the activity of these various ion channels can cause alterations in the cell membrane potential and the firing patterns of action potentials in electrically excitable cells. Recent data indicate that abnormalities in the function of these ion channels, whether regarding the loss of function or gain of function, are closely related to the mechanisms of many diseases and their pharmacological treatments. These specific diseases include epileptic disorders, different cardiac arrhythmias, and certain endocrine disorders. Therefore, we earnestly hope that researchers in this field will actively publish and share their latest and most interesting findings with us.

Prof. Dr. Sheng-Nan Wu
Guest Editor

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Keywords

  • sodium current
  • potassium current
  • ion channel kinetics
  • excitable cells
  • treatments
  • pathophysiology

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Published Papers (3 papers)

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Research

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16 pages, 3566 KB  
Article
Reanimation of Stored Tissue Biopsies: A Functional Study and Translational Approach
by Veronica Alfano, Gabriele Ruffolo, Antonella Spila, Maria Giovanna Valente, Luigi Sansone, Manuel Belli, Dania Ramadan, Chiara Miele, Luca Garelli, Leonardo Lupacchini, Patrizia Ferroni, Daniela Merlo, Eleonora Palma and Fiorella Guadagni
Int. J. Mol. Sci. 2026, 27(3), 1298; https://doi.org/10.3390/ijms27031298 - 28 Jan 2026
Viewed by 424
Abstract
The availability of biobanked tissues represents an important resource for translational research; however, functional investigations are generally limited to freshly collected samples. To address this limitation, we developed an innovative strategy to restore functional properties of frozen biopsies by microtransplanting patient-derived membrane proteins [...] Read more.
The availability of biobanked tissues represents an important resource for translational research; however, functional investigations are generally limited to freshly collected samples. To address this limitation, we developed an innovative strategy to restore functional properties of frozen biopsies by microtransplanting patient-derived membrane proteins into Xenopus laevis oocytes. This study aimed to recover and characterize the physiological properties of human colon cancer cell membranes and to investigate the role of neurotransmitter-related signaling and ion currents in cancer. Membrane incorporation was assessed by immunohistochemical detection of tumor-specific markers, including carcinoembryonic antigen, together with confocal microscopy and ultrastructural analyses. Functional viability was evaluated using two-electrode voltage clamp recordings to assess endogenous calcium-activated chloride currents and responses to selected neurotransmitters. The successful incorporation of colon cancer membranes was confirmed by specific immunoreactivity and ultrastructural features consistent with cancer cell architecture. Although no functional responses to the tested neurotransmitters were detected, oocytes microinjected with cancer membranes showed a marked reduction or complete suppression in endogenous calcium-activated chloride currents. These findings demonstrate that membrane microtransplantation into Xenopus oocytes is a reliable translational approach to functionally investigate cancer cell membranes from frozen biopsies, and suggest that altered chloride channel activity may represent a baseline for new studies to investigate new potential therapeutic targets for colon cancer. Full article
(This article belongs to the Special Issue Role of Ion Channels in Human Health and Diseases)
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17 pages, 4418 KB  
Article
Increasing Temperature Activates TREK Potassium Currents in Vagal Afferent Neurons from the Nodose Ganglion
by Lola Rueda-Ruzafa, Ana Campos-Ríos, Paula Rivas-Ramírez, Manuela Rodríguez-Castañeda, Salvador Herrera-Pérez and José Antonio Lamas
Int. J. Mol. Sci. 2025, 26(18), 9119; https://doi.org/10.3390/ijms26189119 - 18 Sep 2025
Viewed by 990
Abstract
Temperature homeostasis is controlled by the vagus nerve. Thermal information is collected by thermoreceptors present in the viscera and driven across sensory neurons of the nodose ganglia (NG), which in turn send it to the hypothalamus. While transient receptor potential channels (TRPs) are [...] Read more.
Temperature homeostasis is controlled by the vagus nerve. Thermal information is collected by thermoreceptors present in the viscera and driven across sensory neurons of the nodose ganglia (NG), which in turn send it to the hypothalamus. While transient receptor potential channels (TRPs) are traditionally considered for thermal transduction, TREK channels belonging to the two-pore domain K+ channels family are emerging as thermosensors, but their role in the NG remains understudied. Patch-clamp recordings revealed that increasing the temperature to physiological levels causes a hyperpolarization of the membrane potential followed by a depolarization and, despite physiological temperature increased the firing rate, we have demonstrated that TREK channels might be taking part in the excitability control by counteracting TRPs’ effects. In fact, single-channel experiments revealed an increase in TREK channel open probability and a subsequent rise in their activity in NG neurons. All this indicates that TREK channels, mainly TREK1, may be responsible along with TRPs for the maintenance of the membrane potential at physiological temperature in NG neurons. Full article
(This article belongs to the Special Issue Role of Ion Channels in Human Health and Diseases)
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Review

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23 pages, 3052 KB  
Review
Targeting Nav Channels for Pain Relief: Structural Insights and Therapeutic Opportunities
by Yuzhen Xie, Xiaoshuang Huang, Fangzhou Lu and Jian Huang
Int. J. Mol. Sci. 2026, 27(3), 1180; https://doi.org/10.3390/ijms27031180 - 23 Jan 2026
Viewed by 1750
Abstract
Pain is an unpleasant but essential sensory experience that serves as a protective mechanism, yet it can also manifest maladaptively in a wide range of pathological conditions. Current analgesic strategies rely heavily on opioid medications and non-steroidal anti-inflammatory drugs (NSAIDs); however, concerns regarding [...] Read more.
Pain is an unpleasant but essential sensory experience that serves as a protective mechanism, yet it can also manifest maladaptively in a wide range of pathological conditions. Current analgesic strategies rely heavily on opioid medications and non-steroidal anti-inflammatory drugs (NSAIDs); however, concerns regarding addiction, tolerance, and dose-limiting adverse effects highlight the urgent need for safer and more effective therapeutics. Voltage-gated sodium (Nav) channels, which govern the initiation and propagation of action potentials, have emerged as promising targets for mechanism-based analgesic development. In particular, the Nav1.7–Nav1.9 subtypes have attracted substantial interest owing to their enrichment in the peripheral nervous system—despite broader expression elsewhere—and their central roles in nociception, offering the potential for non-addictive, subtype-selective pain modulation. This review summarizes the physiological roles of these channels in nociception, examines how disease-associated mutations shape pain phenotypes, and highlights recent advances in drug discovery targeting Nav1.7 and Nav1.8. The recent FDA approval of VX-548 (suzetrigine), a first-in-class and highly selective Nav1.8 inhibitor, marks a major milestone that validates peripheral Nav channels as clinically actionable targets for analgesia. We also discuss the remaining challenges and emerging opportunities in the pursuit of next-generation, mechanism-informed analgesics. Full article
(This article belongs to the Special Issue Role of Ion Channels in Human Health and Diseases)
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