scholarly journals EGL-19 and EXP-2 Ion Channels Modelling within C. Elegans Pharyngeal Muscle Cell Allows Reproduction of CA2+ Driven Action Potentials, Both Single Events and Trains

2017 ◽  
Author(s):  
Andrey Yu. Palyanov ◽  
Khristina V. Samoilova ◽  
Natalia V. Palyanova
Keyword(s):  
Ion Channels ◽  
Muscle Cell ◽  
Action Potentials ◽  
Computational Models ◽  
Signal Transmission ◽  
Open Science ◽  
Time Profile ◽  
Simulation Environment ◽  
Pharyngeal Muscle ◽  
C Elegans

One of the current problems at the interface between neuroscience, biophysics, and computational modeling is the reverse-engineering and reproduction of Caenorhabditis elegans using computer simulation. The aim of our research was to develop the computational models and techniques for solving this problem while participating in the international open science OpenWorm Project. We have suggested models of a typical C. elegans neuron and a pharyngeal muscle cell, which were constructed and optimized using the NEURON simulation environment. The available experimental data about EGL-19 and EXP-2 ion channels allowed the model of a muscle to reproduce the action potential time profile correctly. Also, the model of a neuron reproduces quite accurately the mechanism of neural signal transmission based on passive propagation. We believe our models to be promising for better representing the specifics of various nervous and muscular cell classes when adding the corresponding ion channel models. Moreover, they can be used to construct the networks of such elements.

scholarly journals Neuronal and Astrocytic Regulations in Schizophrenia: A Computational Modelling Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Lea Fritschi ◽  
Johanna Hedlund Lindmar ◽  
Florian Scheidl ◽  
Kerstin Lenk
Keyword(s):  
Computational Models ◽  
Glutamate Release ◽  
Signal Transmission ◽  
Computational Modelling ◽  
Atp Release ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Neuronal Network Activity ◽  
Cell Densities ◽  
Synapse Model

According to the tripartite synapse model, astrocytes have a modulatory effect on neuronal signal transmission. More recently, astrocyte malfunction has been associated with psychiatric diseases such as schizophrenia. Several hypotheses have been proposed on the pathological mechanisms of astrocytes in schizophrenia. For example, post-mortem examinations have revealed a reduced astrocytic density in patients with schizophrenia. Another hypothesis suggests that disease symptoms are linked to an abnormality of glutamate transmission, which is also regulated by astrocytes (glutamate hypothesis of schizophrenia). Electrophysiological findings indicate a dispute over whether the disorder causes an increase or a decrease in neuronal and astrocytic activity. Moreover, there is no consensus as to which molecular pathways and network mechanisms are altered in schizophrenia. Computational models can aid the process in finding the underlying pathological malfunctions. The effect of astrocytes on the activity of neuron-astrocyte networks has been analysed with computational models. These can reproduce experimentally observed phenomena, such as astrocytic modulation of spike and burst signalling in neuron-astrocyte networks. Using an established computational neuron-astrocyte network model, we simulate experimental data of healthy and pathological networks by using different neuronal and astrocytic parameter configurations. In our simulations, the reduction of neuronal or astrocytic cell densities yields decreased glutamate levels and a statistically significant reduction in the network activity. Amplifications of the astrocytic ATP release toward postsynaptic terminals also reduced the network activity and resulted in temporarily increased glutamate levels. In contrast, reducing either the glutamate release or re-uptake in astrocytes resulted in higher network activities. Similarly, an increase in synaptic weights of excitatory or inhibitory neurons raises the excitability of individual cells and elevates the activation level of the network. To conclude, our simulations suggest that the impairment of both neurons and astrocytes disturbs the neuronal network activity in schizophrenia.

Hodgkin–Huxley neurons with defective and blocked ion channels

2015 ◽  
Vol 26 (10) ◽  
pp. 1550112 ◽  
Author(s):  
James Christopher S. Pang ◽  
Johnrob Y. Bantang
Keyword(s):  
Ion Channels ◽  
Action Potentials ◽  
Reversal Potential ◽  
Membrane Conductance ◽  
Potassium Ions ◽  
Temporal Response ◽  
Constant Input ◽  
Control Drug ◽  
Channel Control ◽  
Sodium And Potassium

We utilize the original Hodgkin–Huxley (HH) model to consider the effects of defective ion channels to the temporal response of neurons. Statistics of firing rate and inter-spike interval (ISI) reveal that production of action potentials (APs) in neurons is not sensitive to changes in membrane conductance for sodium and potassium ions, as well as to the reversal potential for sodium ions, as long as the relevant parameters do not exceed 13% from their normal levels. We also found that blockage of a critical fraction of either sodium or potassium channels (dependent on constant input current) respectively limits the firing activity or increases spontaneous spiking activity of neurons. Our model may be used to guide experiment designs related to ion channel control drug development.

Abstract 63: Potential Genetic and Pharmacological Protection from Virus-induced Ventricular Arrhythmias and Sudden Cardiac Death

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Nathalie Strutz-eebohm ◽  
Katja Steinke ◽  
Ulrike Henrion ◽  
Matthias Rohbeck ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Ion Channels ◽  
Sudden Cardiac Death ◽  
Action Potentials ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Proper Function ◽  
Channel Trafficking ◽  
Cardiac Ion Channels ◽  
Evolutionary Advantage ◽  
Group B

In patients as well as in mouse models, enteroviral infections, especially Coxsackie group B viruses (CVB1-6), frequently induce ventricular arrhythmias and sudden cardiac death. The cardiac action potential requires proper function of cardiac ion channels. CVB3 alters Kv7.1 channel trafficking potentially leading to changes in action potentials and increasing likelihood of arrhythmias. Genetic variants of cardiac ion channels can cause changes in channel trafficking that may preserve from CVB3 modulations and present an evolutionary advantage. Here, we show that a common polymorphic Kv7.1 channel variant uses alternative trafficking pathways and may thus exert a benefit during CVB3 infections. Genetic and pharmacological disruption of a CVB3-stimulated Serum- and Glucocorticoid inducible Kinase 1 (SGK1) pathways blunts Kv7.1 channel dysfunctions. Our results suggest that escape from CVB3-induced SGK1-stimulation by genetic variation in Kv7.1 may be protective and inhibition of SGK1 may present a pharmacological approach to reduce the pro-arrhythmic risk associated with acute coxsackievirus infections.

An analysis of the response to gut induction in the C. elegans embryo

Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 1227-1236 ◽  
Author(s):  
B. Goldstein
Keyword(s):  
Body Wall ◽  
Cell Lineage ◽  
Muscle Cells ◽  
The Other ◽  
Cell Stage ◽  
Pharyngeal Muscle ◽  
Cell Cycles ◽  
Sister Cell ◽  
C Elegans ◽  
Cell Diversity

Establishment of the gut founder cell (E) in C. elegans involves an interaction between the P2 and the EMS cell at the four cell stage. Here I show that the fate of only one daughter of EMS, the E cell, is affected by this induction. In the absence of the P2-EMS interaction, both E and its sister cell, MS, produce pharyngeal muscle cells and body wall muscle cells, much as MS normally does. By cell manipulations and inhibitor studies, I show first that EMS loses the competence to respond before it divides even once, but P2 presents an inducing signal for at least three cell cycles. Second, induction on one side of the EMS cell usually blocks the other side from responding to a second P2-derived signal. Third, microfilaments and microtubules may be required near the time of the interaction for subsequent gut differentiation. Lastly, cell manipulations in pie-1 mutant embryos, in which the P2 cell is transformed to an EMS-like fate and produces a gut cell lineage, revealed that gut fate is segregated to one of P2's daughters cell-autonomously. The results contrast with previous results from similar experiments on the response to other inductions, and suggest that this induction may generate cell diversity by a different mechanism.

scholarly journals Electrophysiology of Syncytial Smooth Muscle

2019 ◽  
Vol 13 ◽  
pp. 117906951882191 ◽  
Author(s):  
Rohit Manchanda ◽  
Shailesh Appukuttan ◽  
Mithun Padmakumar
Keyword(s):  
Smooth Muscle ◽  
Action Potentials ◽  
Signal Analysis ◽  
Computational Models ◽  
Vas Deferens ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Biophysical Analysis ◽  
Recent Developments ◽  
The Many

As in other excitable tissues, two classes of electrical signals are of fundamental importance to the functioning of smooth muscles: junction potentials, which arise from neurotransmission and represent the initiation of excitation (or in some instances inhibition) of the tissue, and spikes or action potentials, which represent the accomplishment of excitation and lead on to contractile activity. Unlike the case in skeletal muscle and in neurons, junction potentials and spikes in smooth muscle have been poorly understood in relation to the electrical properties of the tissue and in terms of their spatiotemporal spread within it. This owes principally to the experimental difficulties involved in making precise electrical recordings from smooth muscles and also to two inherent features of this class of muscle, ie, the syncytial organization of its cells and the distributed innervation they receive, which renders their biophysical analysis problematic. In this review, we outline the development of hypotheses and knowledge on junction potentials and spikes in syncytial smooth muscle, showing how our concepts have frequently undergone radical changes and how recent developments hold promise in unraveling some of the many puzzles that remain. We focus especially on computational models and signal analysis approaches. We take as illustrative examples the smooth muscles of two organs with distinct functional characteristics, the vas deferens and urinary bladder, while also touching on features of electrical functioning in the smooth muscles of other organs.

Smooth muscle cell-specific TMEM16A deletion does not alter Ca2+ signaling, uterine contraction, gestation length, or litter size in mice†

2019 ◽  
Vol 101 (2) ◽  
pp. 318-327 ◽  
Author(s):  
Mingzi Qu ◽  
Ping Lu ◽  
Karl Bellve ◽  
Kevin Fogarty ◽  
Lawrence Lifshitz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Smooth Muscle Cell ◽  
Litter Size ◽  
Muscle Cell ◽  
Uterine Contraction ◽  
Gestation Length ◽  
Specific Marker ◽  
Myometrial Cells

Abstract Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance, and parturition; thus, identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl− channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found that myometrial cells from TMEM16ASMKO mice generated the same pattern and magnitude in Ca2+ signals upon stimulation with KCl, oxytocin, and PGF2α compared to the isogenic control myometrial cells. At the uterine tissue level, TMEM16A deletion also did not cause detectable changes in either spontaneous or agonist (i.e. KCl, oxytocin, and PGF2α)-induced contractions. Moreover, in vivo the TMEM16ASMKO mice gave birth at full term with the same litter size as genetically identical control mice. Finally, TMEM16A immunostaining in both control and TMEM16ASMKO mice revealed that this protein was highly expressed in the endometrial stroma, but did not co-localize with a smooth muscle specific marker MYH11. Collectively, these results unequivocally demonstrate that TMEM16A does not serve as a pacemaking channel for spontaneous uterine contraction, neither does it function as a depolarizing channel for agonist-evoked uterine contraction. Yet these two functions could underlie the normal gestation length and litter size in the TMEM16ASMKO mice.

scholarly journals Sensing through Non-Sensing Ocular Ion Channels

2020 ◽  
Vol 21 (18) ◽  
pp. 6925
Author(s):  
Meha Kabra ◽  
Bikash Ranjan Pattnaik
Keyword(s):  
Ion Channels ◽  
Visual Processing ◽  
Signal Transmission ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Cone Dystrophy ◽  
Wide Range ◽  
The Impact

Ion channels are membrane-spanning integral proteins expressed in multiple organs, including the eye. In the eye, ion channels are involved in various physiological processes, like signal transmission and visual processing. A wide range of mutations have been reported in the corresponding genes and their interacting subunit coding genes, which contribute significantly to an array of blindness, termed ocular channelopathies. These mutations result in either a loss- or gain-of channel functions affecting the structure, assembly, trafficking, and localization of channel proteins. A dominant-negative effect is caused in a few channels formed by the assembly of several subunits that exist as homo- or heteromeric proteins. Here, we review the role of different mutations in switching a “sensing” ion channel to “non-sensing,” leading to ocular channelopathies like Leber’s congenital amaurosis 16 (LCA16), cone dystrophy, congenital stationary night blindness (CSNB), achromatopsia, bestrophinopathies, retinitis pigmentosa, etc. We also discuss the various in vitro and in vivo disease models available to investigate the impact of mutations on channel properties, to dissect the disease mechanism, and understand the pathophysiology. Innovating the potential pharmacological and therapeutic approaches and their efficient delivery to the eye for reversing a “non-sensing” channel to “sensing” would be life-changing.

scholarly journals The quest for action potentials in C. elegans neurons hits a plateau

2009 ◽  
Vol 12 (4) ◽  
pp. 377-378 ◽  
Author(s):  
Shawn R Lockery ◽  
Miriam B Goodman
Keyword(s):  
Action Potentials ◽  
C Elegans
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