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Modulation of Ion Channels

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

Deadline for manuscript submissions: closed (10 July 2024) | Viewed by 9029

Special Issue Editor

Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
Interests: ion channel physiology; ion channel pharmacology; ion channel biophysics; electrophysiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ion channels play a pivotal role in dictating physiological functions of cells or tissues. The passage of ions such as calcium, potassium, sodium and chloride etc across the impermeable lipid cell membrane controls many cellular processes including cell swelling, cell contraction, nutrient transport, hormone or insulin release, pain signal transmission and so on. Disruption of normal ion channel functions resulting from either a mutation in the gene encoding ion channel or its regulatory proteins or change of membrane lipid environment could cause a multitude of diseases (e.g. hypertension, diabetes, diarrhea, long QT syndrome, epilepsy and cystic fibrosis). Therefore, It is important to understand the fundamental questions on ion channels and develop new tools and techniques for ion channels.

In this special issue, we are dedicated to publishing high-quality papers (either research papers or review papers) covering a wide of range of ion channel topics. In addtion to reporting innovative techniques for ion channel research and new pharmacological knowledge of ion channels, we will highlight novel regulations of ion channels and their roles at all levels. The papers studying structure-function relationship, biophysical characterisation, physiological or pathophysiological roles, pharmacology and new tools of ion channels are all welcomed for this special issue. 

Dr. Jian Shi
Guest Editor

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Keywords

  • ion channel structure
  • ion channel functions
  • ion channel pharmacology
  • ion channel and diseases
  • innovative techniques for ion channel research

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Published Papers (5 papers)

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Research

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16 pages, 1912 KiB  
Article
Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci
by Nesrien M. M. Mohamed, Frances L. Meredith and Katherine J. Rennie
Int. J. Mol. Sci. 2024, 25(16), 8801; https://doi.org/10.3390/ijms25168801 - 13 Aug 2024
Viewed by 630
Abstract
Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac®) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been [...] Read more.
Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac®) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K+ channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K+ currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K+ currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 μM fluoxetine notably reduced K+ currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K+ current and revealed a rapidly activating and inactivating K+ current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K+ currents persisted following application of 100 μM fluoxetine. Additionally, marked inhibition of transient inward Na+ currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC50 values were found to be 40 µM and 32 µM for K+ and Na+ currents, respectively. In contrast, 100 μM fluoxetine had no impact on voltage-dependent K+ currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na+ and K+ conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance. Full article
(This article belongs to the Special Issue Modulation of Ion Channels)
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15 pages, 1832 KiB  
Article
A Possible Role of Tetrodotoxin-Sensitive Na+ Channels for Oxidation-Induced Late Na+ Currents in Cardiomyocytes
by Anja Schneider, Axel Hage, Inês Carvalheira Arnaut Pombeiro Stein, Nils Kriedemann, Robert Zweigerdt and Andreas Leffler
Int. J. Mol. Sci. 2024, 25(12), 6596; https://doi.org/10.3390/ijms25126596 - 15 Jun 2024
Cited by 1 | Viewed by 668
Abstract
An accumulation of reactive oxygen species (ROS) in cardiomyocytes can induce pro-arrhythmogenic late Na+ currents by removing the inactivation of voltage-gated Na+ channels including the tetrodotoxin (TTX)-resistant cardiac α-subunit Nav1.5 as well as TTX-sensitive α-subunits like Nav1.2 and Nav1.3. Here, we [...] Read more.
An accumulation of reactive oxygen species (ROS) in cardiomyocytes can induce pro-arrhythmogenic late Na+ currents by removing the inactivation of voltage-gated Na+ channels including the tetrodotoxin (TTX)-resistant cardiac α-subunit Nav1.5 as well as TTX-sensitive α-subunits like Nav1.2 and Nav1.3. Here, we explored oxidant-induced late Na+ currents in mouse cardiomyocytes and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in HEK 293 cells expressing Nav1.2, Nav1.3, or Nav1.5. Na+ currents in mouse cardiomyocytes and hiPSC-CMs treated with the oxidant chloramine T (ChT) developed a moderate reduction in peak current amplitudes accompanied by large late Na+ currents. While ChT induced a strong reduction in peak current amplitudes but only small persistent currents on Nav1.5, both Nav1.2 and Nav1.3 produced increased peak current amplitudes and large persistent currents following oxidation. TTX (300 nM) blocked ChT-induced late Na+ currents significantly stronger as compared to peak Na+ currents in both mouse cardiomyocytes and hiPSC-CMs. Similar differences between Nav1.2, Nav1.3, and Nav1.5 regarding ROS sensitivity were also evident when oxidation was induced with UVA-light (380 nm) or the cysteine-selective oxidant nitroxyl (HNO). To conclude, our data on TTX-sensitive Na+ channels expressed in cardiomyocytes may be relevant for the generation of late Na+ currents following oxidative stress. Full article
(This article belongs to the Special Issue Modulation of Ion Channels)
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16 pages, 4283 KiB  
Article
Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism
by Xiaoan Wu, Kevin P. Cunningham, Andrew Bruening-Wright, Shilpi Pandey and H. Peter Larsson
Int. J. Mol. Sci. 2024, 25(8), 4309; https://doi.org/10.3390/ijms25084309 - 13 Apr 2024
Viewed by 929
Abstract
Voltage-gated potassium (Kv) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels share similar structures but have opposite gating polarity. Kv channels have a strong coupling (>109) between the voltage sensor (S4) and the activation gate: when S4s are activated, the gate is [...] Read more.
Voltage-gated potassium (Kv) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels share similar structures but have opposite gating polarity. Kv channels have a strong coupling (>109) between the voltage sensor (S4) and the activation gate: when S4s are activated, the gate is open to >80% but, when S4s are deactivated, the gate is open <10−9 of the time. Using noise analysis, we show that the coupling between S4 and the gate is <200 in HCN channels. In addition, using voltage clamp fluorometry, locking the gate open in a Kv channel drastically altered the energetics of S4 movement. In contrast, locking the gate open or decreasing the coupling between S4 and the gate in HCN channels had only minor effects on the energetics of S4 movement, consistent with a weak coupling between S4 and the gate. We propose that this loose coupling is a prerequisite for the reversed voltage gating in HCN channels. Full article
(This article belongs to the Special Issue Modulation of Ion Channels)
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Review

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32 pages, 676 KiB  
Review
Flavonoids as Modulators of Potassium Channels
by Monika Richter-Laskowska, Paulina Trybek, Domenico Vittorio Delfino and Agata Wawrzkiewicz-Jałowiecka
Int. J. Mol. Sci. 2023, 24(2), 1311; https://doi.org/10.3390/ijms24021311 - 9 Jan 2023
Cited by 12 | Viewed by 3703
Abstract
Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular [...] Read more.
Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. One of the recent trends in molecular pharmacology is the evaluation of the therapeutic potential of natural compounds and their derivatives, which can exhibit high specificity and effectiveness. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health. Here, we focus on presenting the current state of knowledge about the possibilities of modulation of particular types of potassium channels by different flavonoids. Additionally, the biological meaning of the flavonoid-mediated changes in the activity of K+ channels will be outlined. Finally, novel promising directions for further research in this area will be proposed. Full article
(This article belongs to the Special Issue Modulation of Ion Channels)
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Other

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7 pages, 798 KiB  
Brief Report
Piezo1 Activation Prevents Spheroid Formation by Malignant Melanoma SK-MEL-2 Cells
by Valeria Y. Vasileva, Zuleikha M. Khairullina and Vladislav I. Chubinskiy-Nadezhdin
Int. J. Mol. Sci. 2023, 24(21), 15703; https://doi.org/10.3390/ijms242115703 - 28 Oct 2023
Cited by 1 | Viewed by 1198
Abstract
Melanoma is a highly aggressive type of skin cancer produced through the malignant transformation of melanocytes, and it is usually associated with a poor prognosis. Clinically, melanoma has several stages associated with migration and invasion of the cells through the skin’s layers, the [...] Read more.
Melanoma is a highly aggressive type of skin cancer produced through the malignant transformation of melanocytes, and it is usually associated with a poor prognosis. Clinically, melanoma has several stages associated with migration and invasion of the cells through the skin’s layers, the rapid spreading of cells and the formation of tumors in multiple organs. The main problem is the emergence of resistance in melanoma to the applied methods of treatment; thus, it is of primary importance to find more crucial signaling pathways that control the progression of this type of cancer and could be targeted to prevent melanoma spreading. Here, we uncover novel aspects of the role of the mechanosensitive ion channel Piezo1 in melanoma tumor formation. Using a combinative approach, we showed the functional expression of mechanosensitive Piezo1 channels in the aggressive human melanoma SK-MEL-2 cell line. We found that chemical activation of Piezo1 by its agonist, Yoda1, prevents melanoma spheroid formation; thus, Piezo1 could be a potential target for selective modulation aimed at the prevention of melanoma development. Full article
(This article belongs to the Special Issue Modulation of Ion Channels)
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