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

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3503

Special Issue Editor


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Guest Editor
Department of Health Science, Laboratory of Physiology and Neuropharmacology, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy
Interests: synaptic plasticity; NMDAreceptor; autism; endothelial cell; neurovascular coupling; Ca2+ signaling; nitric oxide

Special Issue Information

Dear Colleagues,

The human body relies on a delicate balance of various elements, including the precise movement of ions, electrically charged atoms, or molecules, across cell membranes. This critical task requires two crucial players: ion channels and transporters. An intricate network of membrane proteins orchestrates the flow of ions, dictating their entry and exit from cells and their release or sequestration by endogenous organelles. This meticulously controlled movement underpins numerous physiological processes, forming the very foundation of human health. Ion channels act as selective pores, opening and closing in response to various stimuli like voltage changes or the presence of specific molecules. They allow specific ions, like sodium, potassium, chloride, and calcium, to pass through the membrane, generating electrical signals and enabling communication within and between cells. In addition, water channels, known as aquaporin, are pivotal to fine-tune cellular volume during osmotic challenges. On the other hand, transporters actively move ions and solutes according to or against their concentration gradient, ensuring their proper distribution and controlling their concentration within cells. This precise control is vital for maintaining homeostasis, the stable internal environment required for cellular function. Transporters also play a key role in nutrient absorption, facilitating the uptake of essential molecules from the gut into the bloodstream for distribution throughout the body. The importance of ion channels and transporters cannot be overstated. Their proper function is vital for countless physiological processes, including synaptic transmission and plasticity, muscle contraction, fluid balance, secretion, and absorption. When these proteins malfunction, it can lead to a cascade of consequences, disrupting the delicate cellular equilibrium and causing various illnesses. Therefore, understanding the intricacies of ion channels and transporters is critical for comprehending human health and disease. The following sections will explore the specific roles these proteins play in various diseases and the potential for therapeutic interventions based on this knowledge.

I am pleased to invite you to participate in this Special Issue. Experimental papers and up-to-date review articles are all welcome.

Dr. Teresa Soda
Guest Editor

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Keywords

  • ion channels
  • transporters
  • ion pumps
  • voltage-gated channels
  • ionotropic receptors
  • TRP channels
  • store-operated channels
  • Piezo channels
  • NALCN channels
  • inositol-1,4,5-receptors
  • ryanodine receptors
  • two-pore channels
  • synaptic transmission
  • channelopathies
  • neurodegenerative disorders
  • cardiovascular disorders

Published Papers (3 papers)

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Research

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13 pages, 3173 KiB  
Article
Chronic Mexiletine Administration Increases Sodium Current in Non-Diseased Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
by Giovanna Nasilli, Arie O. Verkerk, Molly O’Reilly, Loukia Yiangou, Richard P. Davis, Simona Casini and Carol Ann Remme
Biomedicines 2024, 12(6), 1212; https://doi.org/10.3390/biomedicines12061212 - 29 May 2024
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Abstract
A sodium current (INa) reduction occurs in the setting of many acquired and inherited conditions and is associated with cardiac conduction slowing and increased arrhythmia risks. The sodium channel blocker mexiletine has been shown to restore the trafficking of mutant sodium [...] Read more.
A sodium current (INa) reduction occurs in the setting of many acquired and inherited conditions and is associated with cardiac conduction slowing and increased arrhythmia risks. The sodium channel blocker mexiletine has been shown to restore the trafficking of mutant sodium channels to the membrane. However, these studies were mostly performed in heterologous expression systems using high mexiletine concentrations. Moreover, the chronic effects on INa in a non-diseased cardiomyocyte environment remain unknown. In this paper, we investigated the chronic and acute effects of a therapeutic dose of mexiletine on INa and the action potential (AP) characteristics in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of a healthy individual. Control hiPSC-CMs were incubated for 48 h with 10 µM mexiletine or vehicle. Following the wash-out of mexiletine, patch clamp analysis and immunocytochemistry experiments were performed. The incubation of hiPSC-CMs for 48 h with mexiletine (followed by wash-out) induced a significant increase in peak INa of ~75%, without any significant change in the voltage dependence of (in)activation. This was accompanied by a significant increase in AP upstroke velocity, without changes in other AP parameters. The immunocytochemistry experiments showed a significant increase in membrane Nav1.5 fluorescence following a 48 h incubation with mexiletine. The acute re-exposure of hiPSC-CMs to 10 µM mexiletine resulted in a small but significant increase in AP duration, without changes in AP upstroke velocity, peak INa density, or the INa voltage dependence of (in)activation. Importantly, the increase in the peak INa density and resulting AP upstroke velocity induced by chronic mexiletine incubation was not counteracted by the acute re-administration of the drug. In conclusion, the chronic administration of a clinically relevant concentration of mexiletine increases INa density in non-diseased hiPSC-CMs, likely by enhancing the membrane trafficking of sodium channels. Our findings identify mexiletine as a potential therapeutic strategy to enhance and/or restore INa and cardiac conduction. Full article
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Review

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34 pages, 3310 KiB  
Review
Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age
by Valentina Brunetti, Teresa Soda, Roberto Berra-Romani, Giovambattista De Sarro, Germano Guerra, Giorgia Scarpellino and Francesco Moccia
Biomedicines 2024, 12(4), 880; https://doi.org/10.3390/biomedicines12040880 - 16 Apr 2024
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Abstract
Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca2+ entry and activity-dependent change in the strength of synaptic transmission, [...] Read more.
Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca2+ entry and activity-dependent change in the strength of synaptic transmission, as well as by metabotropic glutamate receptors (mGluRs), which mediate slower postsynaptic responses through the recruitment of second messenger systems. A wealth of evidence reported over the last three decades has shown that this dogmatic subdivision between iGluRs and mGluRs may not reflect the actual physiological signaling mode of the iGluRs, i.e., α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA) receptors (AMPAR), kainate receptors (KARs), and N-methyl-D-aspartate (NMDA) receptors (NMDARs). Herein, we review the evidence available supporting the notion that the canonical iGluRs can recruit flux-independent signaling pathways not only in neurons, but also in brain astrocytes and cerebrovascular endothelial cells. Understanding the signaling versatility of iGluRs can exert a profound impact on our understanding of glutamatergic synapses. Furthermore, it may shed light on novel neuroprotective strategies against brain disorders. Full article
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16 pages, 2385 KiB  
Review
Transporters, Ion Channels, and Junctional Proteins in Choroid Plexus Epithelial Cells
by Masaki Ueno, Yoichi Chiba, Ryuta Murakami, Yumi Miyai, Koichi Matsumoto, Keiji Wakamatsu, Toshitaka Nakagawa, Genta Takebayashi, Naoya Uemura, Ken Yanase and Yuichi Ogino
Biomedicines 2024, 12(4), 708; https://doi.org/10.3390/biomedicines12040708 - 22 Mar 2024
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Abstract
The choroid plexus (CP) plays significant roles in secreting cerebrospinal fluid (CSF) and forming circadian rhythms. A monolayer of epithelial cells with tight and adherens junctions of CP forms the blood–CSF barrier to control the movement of substances between the blood and ventricles, [...] Read more.
The choroid plexus (CP) plays significant roles in secreting cerebrospinal fluid (CSF) and forming circadian rhythms. A monolayer of epithelial cells with tight and adherens junctions of CP forms the blood–CSF barrier to control the movement of substances between the blood and ventricles, as microvessels in the stroma of CP have fenestrations in endothelial cells. CP epithelial cells are equipped with several kinds of transporters and ion channels to transport nutrient substances and secrete CSF. In addition, junctional components also contribute to CSF production as well as blood–CSF barrier formation. However, it remains unclear how junctional components as well as transporters and ion channels contribute to the pathogenesis of neurodegenerative disorders. In this manuscript, recent findings regarding the distribution and significance of transporters, ion channels, and junctional proteins in CP epithelial cells are introduced, and how changes in expression of their epithelial proteins contribute to the pathophysiology of brain disorders are reviewed. Full article
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