scholarly journals Ion Channel Dysfunction and Neuroinflammation in Migraine and Depression

2021 ◽  
Vol 12 ◽  
Author(s):  
Emine Eren-Koçak ◽  
Turgay Dalkara
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Energy Homeostasis ◽  
Inflammatory Signaling ◽  
Pannexin 1 ◽  
Significant Heritability ◽  
Homeostatic Function ◽  
And Function ◽  
Excitability Of Neurons

Migraine and major depression are debilitating disorders with high lifetime prevalence rates. Interestingly these disorders are highly comorbid and show significant heritability, suggesting shared pathophysiological mechanisms. Non-homeostatic function of ion channels and neuroinflammation may be common mechanisms underlying both disorders: The excitation-inhibition balance of microcircuits and their modulation by monoaminergic systems, which depend on the expression and function of membrane located K+, Na+, and Ca+2 channels, have been reported to be disturbed in both depression and migraine. Ion channels and energy supply to synapses not only change excitability of neurons but can also mediate the induction and maintenance of inflammatory signaling implicated in the pathophysiology of both disorders. In this respect, Pannexin-1 and P2X7 large-pore ion channel receptors can induce inflammasome formation that triggers release of pro-inflammatory mediators from the cell. Here, the role of ion channels involved in the regulation of excitation-inhibition balance, synaptic energy homeostasis as well as inflammatory signaling in migraine and depression will be reviewed.

scholarly journals Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis

2020 ◽  
Author(s):  
Huascar Pedro Ortuste Quiroga ◽  
Shingo Yokoyama ◽  
Massimo Ganassi ◽  
Kodai Nakamura ◽  
Tomohiro Yamashita ◽  
...  
Keyword(s):  
Ion Channel ◽  
Molecular Mechanisms ◽  
Myoblast Fusion ◽  
Mechanical Stimuli ◽  
Muscle Satellite Cell ◽  
Myotube Formation ◽  
Mechanosensitive Ion Channel ◽  
And Function ◽  
Sirna Knockdown

AbstractMechanical stimuli such as stretch and resistance training are essential to regulate growth and function of skeletal muscle. However, the molecular mechanisms involved in sensing mechanical stress remain unclear. Here, the purpose of this study was to investigate the role of the mechanosensitive ion channel Piezo1 during myogenic progression. Muscle satellite cell-derived myoblasts and myotubes were modified with stretch, siRNA knockdown and agonist-induced activation of Piezo1. Direct manipulation of Piezo1 modulates terminal myogenic progression. Piezo1 knockdown suppressed myoblast fusion during myotube formation and maturation. This was accompanied by downregulation of the fusogenic protein Myomaker. Piezo1 knockdown also lowered Ca2+ influx in response to stretch. Conversely Piezo1 activation stimulated fusion and increased Ca2+ influx in response to stretch. These evidences indicate that Piezo1 is essential for myotube formation and maturation, which may have implications for msucular dystrophy prevention through its role as a mechanosensitive Ca2+ channel.

scholarly journals Site-specific deacylation by ABHD17a controls BK channel splice variant activity

2020 ◽  
Vol 295 (49) ◽  
pp. 16487-16496 ◽  
Author(s):  
Heather McClafferty ◽  
Hamish Runciman ◽  
Michael J. Shipston
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Membrane Trafficking ◽  
Transmembrane Protein ◽  
Surface Expression ◽  
Bk Channels ◽  
Bk Channel ◽  
Site Specific ◽  
And Function ◽  
A Site

S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.

scholarly journals Phosphorylation-Dependent Regulation of Ryanodine Receptors

2001 ◽  
Vol 153 (4) ◽  
pp. 699-708 ◽  
Author(s):  
Steven O. Marx ◽  
Steven Reiken ◽  
Yuji Hisamatsu ◽  
Marta Gaburjakova ◽  
Jana Gaburjakova ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Rapid Identification ◽  
Calcium Release Channels ◽  
Macromolecular Complexes ◽  
Protein Binding Sites ◽  
Skeletal Muscle Contraction

Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.

scholarly journals Non-genomic effects of steroid hormones: role of ion channels

2019 ◽  
pp. 3-12 ◽  
Author(s):  
Darya Y. Straltsova ◽  
Maryia A. Charnysh ◽  
Palina V. Hryvusevich ◽  
Vadim V. Demidchik
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Steroid Hormones ◽  
Plant Cells ◽  
Membrane Receptors ◽  
Physiological Effects ◽  
Genomic Effects

In animals, steroid hormones can act using genomic and non-genomic mechanisms. Plant steroid hormones, brassinosteroids, are capable of inducing the expression of some gene ensembles, however their non-genomic pathways for triggering the physiological effects are still unclear. In this paper, we propose the hypothesis on existence of brassinosteroid non-genomic effects in plant cells. This non-genomic pathway could due to modulation of ion channel activities and modification of membrane receptors.

scholarly journals Conserved His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

2020 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Ion Selectivity ◽  
Fear Memory ◽  
Amino Terminus ◽  
Ion Permeation ◽  
Structural Explanation ◽  
Cryo Electron Microscopy ◽  
Acid Sensing Ion Channels ◽  
And Function

ABSTRACTAcid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here we extract full-length chicken ASIC1a (cASIC1a) from cell membranes using styrene maleic acid (SMA) copolymer, yielding structures of ASIC1a channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1a that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

Actin dynamics as critical ion channel regulator: ENaC and Piezo in focus

2021 ◽  
Author(s):  
Elena A. Morachevskaya ◽  
Anastasia V. Sudarikova
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Dynamic Balance ◽  
Cell Volume Regulation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Assembly ◽  
Excitable Cells ◽  
Physiological Processes

Ion channels in plasma membrane play a principal role in different physiological processes, including cell volume regulation, signal transduction and modulation of membrane potential in living cells. Actin-based cytoskeleton, which exists in a dynamic balance between monomeric and polymeric forms (globular and fibrillar actin), can be directly or indirectly involved in various cellular responses including modulation of ion channel activity. In this mini-review, we present an overview of the role of submembranous actin dynamics in the regulation of ion channels in excitable and non-excitable cells. Special attention is focused on the important data about the involvement of actin assembly/disassembly and some actin-binding proteins in the control of the Epithelial Na+ Channel (ENaC) and mechanosensitive Piezo channels whose integral activity has potential impact on membrane transport and multiple coupled cellular reactions. Growing evidence suggests that actin elements of the cytoskeleton can represent a "converging point" of various signaling pathways modulating the activity of ion transport proteins in cell membranes.

scholarly journals Role of Neurotrophins in the Development and Function of Neural Circuits That Regulate Energy Homeostasis

2012 ◽  
Vol 48 (3) ◽  
pp. 654-659 ◽  
Author(s):  
Samira Fargali ◽  
Masato Sadahiro ◽  
Cheng Jiang ◽  
Amy L. Frick ◽  
Tricia Indall ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Neural Circuits ◽  
And Function

scholarly journals Regulation of food intake by mechanosensory ion channels in enteric neurons

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
William H Olds ◽  
Tian Xu
Keyword(s):  
Ion Channels ◽  
Food Intake ◽  
Ion Channel ◽  
Weight Control ◽  
Energy Homeostasis ◽  
Therapeutic Strategy ◽  
Molecular Genetic ◽  
Enteric Neurons ◽  
Specific Subset ◽  
Molecular Genetic Evidence

Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activities of a specific subset of enteric neurons, the posterior enteric neurons (PENs), results in sixfold changes in food intake. Deficiency of the mechanosensory ion channel PPK1 gene or RNAi knockdown of its expression in the PENS result in a similar increase in food intake, which can be rescued by expression of wild-type PPK1 in the same neurons. Finally, pharmacological inhibition of the mechanosensory ion channel phenocopies the result of genetic interrogation. Together, our study provides the first molecular genetic evidence that mechanosensory ion channels in the enteric neurons are involved in regulating feeding, offering an enticing alternative to current therapeutic strategy for weight control.

scholarly journals Influence of miR-221/222 on cardiomyocyte calcium handling and function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Knyrim ◽  
Sindy Rabe ◽  
Claudia Grossmann ◽  
Michael Gekle ◽  
Barbara Schreier
Keyword(s):  
Ion Channel ◽  
Current Density ◽  
Systolic Dysfunction ◽  
Calcium Handling ◽  
Electrical Remodeling ◽  
Ion Channel Regulation ◽  
Neonatal Cardiomyocytes ◽  
And Function ◽  
The Impact

Abstract Background Cardiovascular disease is the leading cause of death worldwide. Cardiac electrical remodeling including altered ion channel expression and imbalance of calcium homeostasis can have detrimental effects on cardiac function. While it has been extensively reported that miR-221/222 are involved in structural remodeling, their role in electrical remodeling still has to be evaluated. We previously reported that subunits of the L-type Ca2+ channel (LTCC) are direct targets of miR-221/222. Furthermore, HL-1 cells transfected with miR-221 or -222 mimics showed a reduction in LTCC current density while the voltage-dependence of activation was not altered. The aim of the present study was to determine the influence of miR-221/222 on cardiomyocyte calcium handling and function. Results Transient transfection of HL-1 cells with miR-221/222 mimics led to slower depolarization-dependent Ca2+ entry and increased proportion of non-responding cells. Angiotensin II-induced Ca2+ release from the SR was not affected by miR-221/222. In miR-222-transfected neonatal cardiomyocytes the isoprenaline-induced positive inotropic effect on the intracellular Ca2+ transient was lost and the positive chronotropic effect on spontaneous beating activity was strongly reduced. This could have severe consequences for cardiomyocytes and could lead to a reduced contractility and systolic dysfunction of the whole heart. Conclusions This study adds a new role of miR-221/222 in cardiomyocytes by showing the impact on β-adrenergic regulation of LTCC function, calcium handling and beating frequency. Together with the previous report that miR-221/222 reduce GIRK1/4 function and LTCC current density, it expands our knowledge about the role of these miRs on cardiac ion channel regulation.

Basic Cardiac Electrophysiology

2013 ◽  
pp. 171-190
Author(s):  
Hon-Chi Lee ◽  
Arshad Jahangir
Keyword(s):  
Ion Channels ◽  
Cardiac Arrhythmias ◽  
Action Potentials ◽  
Cardiac Electrophysiology ◽  
Structure And Function ◽  
Learning Objectives ◽  
Cardiac Ion Channels ◽  
Cardiac Action ◽  
And Function

The learning objectives of this chapter are to review some basic electrophysiologic concepts that are useful for the clinician. These include 1) the structure and function of cardiac ion channels; 2) the role of ion channels in the generation of cardiac action potentials; 3) the mechanisms of cardiac arrhythmias; and 4) inherited and acquired channelopathies.

Sign in / Sign up

Export Citation Format

Share Document