The Effects of Ion Channel Inhibitors on the Generation of Electrical Impulses in Right Atrial Pacemaker Cells of 10-Day-Old Chicken Embryos

Abstract Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X7 receptors and Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma.

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Specificity of ion channel inhibitors for the maxi cation channel in rye root plasma membranes

Journal of Experimental Botany ◽

10.1093/jxb/47.5.713 ◽

1996 ◽

Vol 47 (5) ◽

pp. 713-716 ◽

Cited By ~ 15

Author(s):

Philip J. White

Keyword(s):

Ion Channel ◽

Plasma Membranes ◽

Cation Channel ◽

Ion Channel Inhibitors

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From ionic to cellular variability in human atrial myocytes: an integrative computational and experimental study

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00477.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. H895-H916 ◽

Cited By ~ 14

Author(s):

Anna Muszkiewicz ◽

Xing Liu ◽

Alfonso Bueno-Orovio ◽

Brodie A. J. Lawson ◽

Kevin Burrage ◽

...

Keyword(s):

Ion Channel ◽

Phenotypic Variability ◽

Right Atrial ◽

Resting Potential ◽

Generic Model ◽

Atrial Myocytes ◽

Human Atrial Myocytes ◽

Human Cardiomyocytes ◽

Atrial Electrophysiology ◽

The Impact

Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions, computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and subcellular ionic densities on Ca2+ transient dynamics. Results showed that 1) variability in APs and ionic densities is large, even within an apparently homogenous patient cohort, and translates into ±100% variation in ionic conductances; 2) experimentally calibrated populations of models with wide variations in ionic densities yield APs overlapping with those obtained experimentally, even if AP characteristics of the original generic model differed significantly from experimental APs; 3) model calibration with AP recordings restricts the variability in ionic densities affecting upstroke and resting potential, but redundancy in repolarization currents admits substantial variability in ionic densities; and 4) model populations constrained with experimental APs and ionic densities exhibit three Ca2+ transient phenotypes, differing in intracellular Ca2+ handling and Na+/Ca2+ membrane extrusion. These findings advance our understanding of the impact of variability in human atrial electrophysiology. NEW & NOTEWORTHY Variability in human atrial electrophysiology is investigated by integrating for the first time cellular-level and ion channel recordings in computational electrophysiological models. Ion channel calibration restricts current densities but not cellular phenotypic variability. Reduced Na+/Ca2+ exchanger is identified as a primary mechanism underlying diastolic Ca2+ fluctuations in human atrial myocytes.

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Efficacy, Mechanism and Antiviral Resistance of Neuraminidase Inhibitors and Adamantane against Avian Influenza

Indonesian Bulletin of Animal and Veterinary Sciences ◽

10.14334/wartazoa.v29i2.1951 ◽

2019 ◽

Vol 29 (2) ◽

pp. 61

Author(s):

Dyah Ayu Hewajuli ◽

NLPI Dharmayanti

Keyword(s):

Avian Influenza ◽

Ion Channel ◽

Influenza A ◽

Influenza Infection ◽

Antiviral Drug ◽

Neuraminidase Inhibitor ◽

M2 Protein ◽

New Variant ◽

Amantadine Resistance ◽

Ion Channel Inhibitors

Vaccination and antiviral drug are often used to control influenza. However, the effectiveness of vaccine was impaired due to the emergence of new variant of virus strain. Antiviral drug consists of prophylactic and curative substances, namely M2 ion channel inhibitors (adamantane; amantadine and rimantadine) and neuraminidase (NA) inhibitors (NAIs; oseltamivir, zanamivir, peramivir, laninamivir). The synthesis and modification of antiviral neuraminidase (NA) inhibitors (NAIs) and adamantanes increased the antiviral effectiveness. The mechanism of the neuraminidase inhibitor is to prevent influenza infection by inhibiting the release of the virus from internal cells. Adamantane is antiviral drug that selectively inhibits the flow of H+ ions through M2 protein to prevent the uncoating virus particles getting into the endosome. The substitution of (H275Y, S247N, I223L, K150N, R292K, I222T, R152K, R118K, E119V) on NA protein caused resistance of avian influenza virus against the neuraminidase inhibitor. The combination of mutations (S247N, I223L, K150N) increased the resistance of influenza A (H5N1) virus. The diffusion of adamantane resistance varies among HA subtypes, the species of host, the period of isolation, and region. Mutations at residues of 26, 27, 30, 31 or 34 transmembrane M2 protein caused adamantane resistance. The unique substitution (V27I) of M2 protein of clade 2.3.2 H5N1 subtype isolated in Indonesia in 2016 has been contributed to the amantadine resistance. Antiviral combination of M2 ion channel inhibitors and neuraminidase (NA) inhibitors is effective treatments for the resistance.

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