Neuromodulation-dependent regulation of coordinated patterns of gene expression in motor neurons of the stomatogastric ganglion

2012 ◽  
Author(s):  
◽  
Simone Temporal
Keyword(s):  
Gene Expression ◽  
Ion Channels ◽  
Potassium Channels ◽  
Calcium Channels ◽  
Ion Channel ◽  
Mrna Expression ◽  
Stomatogastric Ganglion ◽  
Muscarinic Agonist ◽  
Burst Frequency ◽  
Network Function

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The pyloric network of the crustacean stomatogastric ganglion (STG) is a central pattern generator that requires descending modulation for normal ongoing rhythmic activity. However, the pyloric rhythm is capable of functional recovery after removal of descending inputs. We used the STG to determine whether or not correlated mRNA ion channels are dependent on neuromodulation. Our hypothesis is that relationships between ion channels are dependent on neuromodulation, not activity. To investigate this, we first measured mRNA expression levels of three calcium channels (Ca1A, Ca1D and T-type-related channel) and two potassium channels (shal and shab), of PD cells to investigate how channel transcription may be modified to influence recovery of burst activity. We collected single PD neurons from both recovered and time-matched control preparations and quantified channel transcript levels with quantitative real-time RT-PCR. There was widespread correlation between all three calcium channels and the two potassium channels in PD cells from intact networks. Specifically, the strongest relationships were between all three calcium channels and the shal channel, which carries an A-type transient potassium current (p[less-than]0.005; R2[greater-than]0.5). Furthermore, our results show that following recovery, there are no significant changes in overall mRNA abundance across all channel types. However, there was a striking lack of any correlation between measured channel types in PD cells following recovery. These results indicate that recovered, decentralized networks do not regain rhythmicity simply by increasing or decreasing mRNA expression for a given channel or channels. In order to determine whether ion channel correlations are dependent on neuromodulation or activity, we decoupled neuromodulatory and activity inputs. We found that preparations with neuromodulatory inputs maintained relationships between mRNA channels while activity input alone did not. Further, addition of pilocarpine, the muscarinic agonist and modulator, to decentralized preparations maintained the same correlations as those found in preparations that only had neuromodulatory input. To determine whether loss of correlations affected network function, we compared the pyloric burst frequency of the different conditions. We found that the pyloric burst frequency decreased under conditions that lost correlations between ion channels due to the removal of neuromodulation. Together, these results indicate that neuromodulation maintains ion channel correlations, which are important to proper network function. They also suggest a possible novel role of neuromodulation in the regulation of gene expression.

scholarly journals Panama: A tool for ion channel biophysics simulation

2018 ◽  
Author(s):  
Anuj Guruacharya
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Calcium Channels ◽  
Ion Channel ◽  
Chloride Channels ◽  
High Threshold ◽  
Spreadsheet Program ◽  
Online Tool ◽  
Voltage Gated ◽  
Web App

I have created an online tool and an R library that simulates biophysics of voltage-gated ion channels. It is made publicly available as an R library called Panama at github.com/anuj2054/panama and as a web app at neuronsimulator.com. A need for such a tool was observed after surveying available software packages. I found that the available packages are either not robust enough to simulate multiple ion channels, too complicated, usable only as desktop software, not optimized for mobile devices, not interactive, lacking intuitive graphical controls, or not appropriate for undergraduate education. My app simulates the physiology of 11 different channels - voltage-gated sodium, potassium, and chloride channels; channels causing A-current, M-current, and After-HyperPolarization (AHP) current; calcium-activated potassium channels; low threshold T type calcium channels and high threshold L type calcium channels; leak sodium and leak potassium channels. It can simulate these channels under both current clamp and voltage clamp conditions. As we change the input values on the app, the output can be instantaneously visualized on the web browser and downloaded as a data table to be further analyzed in a spreadsheet program. The app is a first of its kind, mobile-friendly and touch-screen-friendly online tool that can be used to teach undergraduate neuroscience classes. It can also be used by researchers on their local computers as part of an R library. It has intuitive touch-optimized controls, instantaneous graphical output, and yet is pedagogically robust for education and casual research purposes.Neuroscience education, ion channel biophysics, Hodgkin-Huxley simulation, web app for neuroscience

Speed and Noise of Neural Membranes: Ion Channel Limitations to Visual Information Transmission

Perception ◽  
1997 ◽  
Vol 26 (1_suppl) ◽  
pp. 38-38
Author(s):  
M Weckström
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Cell Membrane ◽  
Ion Channel ◽  
Visual Information ◽  
Electrical Response ◽  
Channel Noise ◽  
Maximum Speed ◽  
Voltage Response ◽  
Neural Noise

In dim light, photoreceptor cells and subsequent neural elements typically show high absolute sensitivity, implying that both phototransduction and synaptic transmission work at a high gain and even a single photon may produce a large electrical response. However, when there is more light, rapid adaptation at several levels of signal processing ensures that the information channel is not congested, but optimally filled with relevant voltage responses. All this is achieved by carefully tuned mechanisms that include several types of ion channels in the cell membrane. These ion-channel mechanisms have been thoroughly investigated in a few species of invertebrates and vertebrates, and some general principles are being revealed. The membrane capacitance and the resistance of the cell together define the time constant of the membrane, thus the maximum speed for building up a voltage response to light. Both in vertebrate cones and in insect microvillar photoreceptors, phototransduction takes place in an enlarged part of the cell membrane, which implies a large capacitance. This can be counteracted by making the membrane more leaky by opening more ion channels. In insect photoreceptors several types of potassium channels have been identified that perform exactly this kind of function. The types of channels vary according to the required speed of phototransduction, ie depending on the life style of the animal. In diurnal dipteran insects the potassium channels are typically of the slowly inactivating type. This channel type regulates the cell impedance according to the depolarisation caused by light stimulation. In insects active in dim environments, the potassium channels found have been predominantly rapidly inactivating. The function of this type of channels is currently under debate. In vertebrate photoreceptors several potassium channel types, including channels sensitive to intracellular calcium and pH, are expressed in the inner segments and modulate photoresponses. Opening and closing of the potassium channels also generates neural noise and thus degrades the signal-to-noise ratio (SNR). However, if the gain of phototransduction is high enough, the dominant noise comes from photon fluctuations, or from the biochemical transduction machinery, or—in some situations—from spontaneous photon-like events. Channel noise is then insignificant by comparison. Thus the optimisation of the SNR is a trade-off between bandwidth (ie speed) and amplification of the signal, and here the voltage-gated potassium channels are of prime importance.

Pain-associated Mediators and Axon Pathfinders in Fibromyalgia Skin Cells

2019 ◽  
Vol 47 (1) ◽  
pp. 140-148 ◽  
Author(s):  
Dimitar Evdokimov ◽  
Luisa Kreß ◽  
Philine Dinkel ◽  
Johanna Frank ◽  
Claudia Sommer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ion Channels ◽  
Ion Channel ◽  
Axon Guidance ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Fiber Density ◽  
Skin Cells ◽  
Intraepidermal Nerve Fiber Density ◽  
Skin Punch Biopsy

Objective.To investigate whether the expression of cytokine, nociception-associated ion channel, and axon guidance genes in patients with skin cell fibromyalgia syndrome (FMS) differs from healthy controls, potentially contributing to pain and small-fiber degeneration in FMS.Methods.We prospectively recruited 128 patients and 26 healthy controls. All study participants underwent neurological examination, and a skin punch biopsy was obtained from the lateral calf and thigh. Skin samples were processed to histologically determine intraepidermal nerve fiber density (IENFD) and for primary fibroblast and keratinocyte cell cultures. Gene expression of selected pro- and antiinflammatory cytokines, nociception-associated ion channels, and axon guidance cues was assessed with quantitative real-time PCR.Results.In fibroblasts, transforming growth factor–ß1 (TGF-ß1) gene expression was higher in patients with FMS compared to controls (calf and thigh: p < 0.001). Also, expression was higher in patients than in controls for these variables: hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (calf: p < 0.01), ephrin-A4 (EFNA4; calf: p < 0.05, thigh: p < 0.001), and ephrin receptor-A4 (EPHA4; thigh: p < 0.05). In keratinocytes, interleukin 10 gene expression was higher in patients with FMS than in controls (thigh: p < 0.05). While no intergroup difference was found for nociception-associated ion channels, EFNA4 and EPHA4 (calf: p < 0.01 each) expression was higher in patients with FMS than in controls. Axon guide expression did not correlate with IENFD.Conclusion.In FMS, skin cells may contribute to cutaneous nociception by differentially expressing membrane-bound and soluble pain mediators and axon pathfinders.

Regulation of ion channel structure and function by reactive oxygen-nitrogen species

2003 ◽  
Vol 285 (6) ◽  
pp. L1184-L1189 ◽  
Author(s):  
Sadis Matalon ◽  
Karin M. Hardiman ◽  
Lucky Jain ◽  
Douglas C. Eaton ◽  
Michael Kotlikoff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ion Channels ◽  
Ion Channel ◽  
Posttranslational Modifications ◽  
Regulation Of Gene Expression ◽  
Reactive Oxygen ◽  
Cellular Level ◽  
Channel Structure ◽  
Nitrogen Species ◽  
Channel Proteins

Ion channels subserve diverse cellular functions. Reactive oxygen and nitrogen species modulate ion channel function by a number of mechanisms including 1) transcriptional regulation of gene expression, 2) posttranslational modifications of channel proteins, i.e. nitrosylation, nitration, and oxidation of key amino acid residues, 3) by altering the gain in other signaling pathways that may in turn lead to changes in channel activity or channel gene expression, and 4) by modulating trafficking or turnover of channel proteins, as typified by oxygen radical activation of NF-kB, with subsequent changes in proteasomal degradation of channel degradation. Regardless of the mechanism, as was discussed in a symposium at the 2003 Experimental Biology Meeting in San Diego, CA, changes in the cellular level of reactive oxygen and nitrogen species can have profound effects on the activity of ion channels and cellular function.

scholarly journals Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

2021 ◽  
Vol 15 ◽  
Author(s):  
Francesca Boscia ◽  
Maria Louise Elkjaer ◽  
Zsolt Illes ◽  
Maria Kukley
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
White Matter ◽  
Ion Channels ◽  
Ion Channel ◽  
Trp Channels ◽  
Ryanodine Receptors ◽  
Altered Expression ◽  
Voltage Gated ◽  
Secondary Progressive

Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K+, Ca2+, Na+, and Cl− channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na+ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na+ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K+ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl− channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.

scholarly journals Consensus channelome of dinoflagellates revealed by transcriptomic analysis sheds light on their physiology

ALGAE ◽  
2021 ◽  
Vol 36 (4) ◽  
pp. 315-326
Author(s):  
Ilya Pozdnyakov ◽  
Olga Matantseva ◽  
Sergei Skarlato
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Ion Channel ◽  
Chloride Channels ◽  
Cation Channels ◽  
Mechanosensitive Channels ◽  
Anion Channels ◽  
Voltage Gated ◽  
Calcium Activated Potassium Channels ◽  
Pore Domain

Ion channels are membrane protein complexes mediating passive ion flux across the cell membranes. Every organism has a certain set of ion channels that define its physiology. Dinoflagellates are ecologically important microorganisms characterized by effective physiological adaptability, which backs up their massive proliferations that often result in harmful blooms (red tides). In this study, we used a bioinformatics approach to identify homologs of known ion channels that belong to 36 ion channel families. We demonstrated that the versatility of the dinoflagellate physiology is underpinned by a high diversity of ion channels including homologs of animal and plant proteins, as well as channels unique to protists. The analysis of 27 transcriptomes allowed reconstructing a consensus ion channel repertoire (channelome) of dinoflagellates including the members of 31 ion channel families: inwardly-rectifying potassium channels, two-pore domain potassium channels, voltage-gated potassium channels (Kv), tandem Kv, cyclic nucleotide-binding domain-containing channels (CNBD), tandem CNBD, eukaryotic ionotropic glutamate receptors, large-conductance calcium-activated potassium channels, intermediate/small-conductance calcium-activated potassium channels, eukaryotic single-domain voltage-gated cation channels, transient receptor potential channels, two-pore domain calcium channels, four-domain voltage-gated cation channels, cation and anion Cys-loop receptors, small-conductivity mechanosensitive channels, large-conductivity mechanosensitive channels, voltage-gated proton channels, inositole-1,4,5- trisphosphate receptors, slow anion channels, aluminum-activated malate transporters and quick anion channels, mitochondrial calcium uniporters, voltage-dependent anion channels, vesicular chloride channels, ionotropic purinergic receptors, animal volage-insensitive cation channels, channelrhodopsins, bestrophins, voltage-gated chloride channels H+/Cl- exchangers, plant calcium-permeable mechanosensitive channels, and trimeric intracellular cation channels. Overall, dinoflagellates represent cells able to respond to physical and chemical stimuli utilizing a wide range of Gprotein coupled receptors- and Ca2+-dependent signaling pathways. The applied approach not only shed light on the ion channel set in dinoflagellates, but also provided the information on possible molecular mechanisms underlying vital cellular processes dependent on the ion transport.

ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders

2020 ◽  
Vol 20 (18) ◽  
pp. 2274-2284
Author(s):  
Faroogh Marofi ◽  
Jalal Choupani ◽  
Saeed Solali ◽  
Ghasem Vahedi ◽  
Ali Hassanzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Osteoblastic Differentiation ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Scheduled Time

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

2019 ◽  
Vol 13 (2) ◽  
pp. 140-148
Author(s):  
Mai Nasser ◽  
Noha M. Hazem ◽  
Amany Atwa ◽  
Amina Baiomy
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Mrna Expression ◽  
Disease Activity Score ◽  
Activity Score ◽  
Tlr2 Expression ◽  
Positive Correlation ◽  
Tlr2 Mrna

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

Sign in / Sign up

Export Citation Format

Share Document