scholarly journals Role of Oxidation-Dependent CaMKII Activation in the Genesis of Abnormal Action Potentials in Atrial Cardiomyocytes: A Simulation Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Na Zhao ◽  
Qince Li ◽  
Haibo Sui ◽  
Henggui Zhang
Keyword(s):  
Oxidative Stress ◽  
Action Potential ◽  
Intracellular Calcium ◽  
Action Potentials ◽  
Cell Model ◽  
Atrial Arrhythmia ◽  
Electrical Excitation ◽  
Calcium Cycling ◽  
Simulation Results ◽  
Camkii Activation

Atrial fibrillation is a common cardiac arrhythmia with an increasing incidence rate. Particularly for the aging population, understanding the underlying mechanisms of atrial arrhythmia is important in designing clinical treatment. Recently, experiments have shown that atrial arrhythmia is associated with oxidative stress. In this study, an atrial cell model including oxidative-dependent Ca2+/calmodulin- (CaM-) dependent protein kinase II (CaMKII) activation was developed to explore the intrinsic mechanisms of atrial arrhythmia induced by oxidative stress. The simulation results showed that oxidative stress caused early afterdepolarizations (EADs) of action potentials by altering the dynamics of transmembrane currents and intracellular calcium cycling. Oxidative stress gradually elevated the concentration of calcium ions in the cytoplasm by enhancing the L-type Ca2+ current and sarcoplasmic reticulum (SR) calcium release. Owing to increased intracellular calcium concentration, the inward Na+/Ca2+ exchange current was elevated which slowed down the repolarization of the action potential. Thus, the action potential was prolonged and the L-type Ca2+ current was reactivated, resulting in the genesis of EAD. Furthermore, based on the atrial single-cell model, a two-dimensional (2D) ideal tissue model was developed to explore the effect of oxidative stress on the electrical excitation wave conduction in 2D tissue. Simulation results demonstrated that, under oxidative stress conditions, EAD hindered the conduction of electrical excitation and caused an unstable spiral wave, which could disrupt normal cardiac rhythm and cause atrial arrhythmia. This study showed the effects of excess reactive oxygen species on calcium cycling and action potential in atrial myocytes and provided insights regarding atrial arrhythmia induced by oxidative stress.

scholarly journals Application of the Optical Method in Experimental Cardiology: Action Potential and Intracellular Calcium Concentration Measurement

2013 ◽  
pp. 125-137 ◽  
Author(s):  
M. RONZHINA ◽  
V. ČMIEL ◽  
O. JANOUŠEK ◽  
J. KOLÁŘOVÁ ◽  
M. NOVÁKOVÁ ◽  
...  
Keyword(s):  
Action Potential ◽  
Intracellular Calcium ◽  
Action Potentials ◽  
Optical Method ◽  
Calcium Concentration ◽  
Fluorescent Dyes ◽  
Concentration Measurement ◽  
Intracellular Calcium Concentration ◽  
Optical Methods ◽  
Contact Electrode

It has been shown that, in addition to conventional contact electrode techniques, optical methods using fluorescent dyes can be successfully used for cardiac signal measurement. In this review, the physical and technical fundamentals of the method are described, as well as the properties of the most common systems for measuring action potentials and intracellular calcium concentration. Special attention is paid to summarizing limitations and trends in developing this method.

Neuroinflammation in Demyelinating Diseases: Oxidative Stress as a Modulator of Glial Cross-Talk

2020 ◽  
Vol 25 (45) ◽  
pp. 4755-4762 ◽  
Author(s):  
Rodrigo Varas ◽  
Fernando C. Ortiz
Keyword(s):  
Oxidative Stress ◽  
Action Potentials ◽  
Cell Interaction ◽  
Demyelinating Diseases ◽  
Signal Molecules ◽  
Oligodendrocyte Precursor Cells ◽  
Cytokines And Chemokines ◽  
Regulatory Aspect ◽  
Saltatory Conduction ◽  
Oligodendrocyte Precursor

: Myelin is a specialized membrane allowing for saltatory conduction of action potentials in neurons, an essential process to achieve the normal communication across the nervous system. Accordingly, in diseases characterized by the loss of myelin and myelin forming cells -oligodendrocytes in the CNS-, patients show severe neurological disabilities. After a demyelinated insult, microglia, astrocytes and oligodendrocyte precursor cells invade the lesioned area initiating a spontaneous process of myelin repair (i.e. remyelination). A preserved hallmark of this neuroinflammatory scenario is a local increase of oxidative stress, where several cytokines and chemokines are released by glial and other cells. This generates an environment that determines cell interaction resulting in oligodendrocyte maturity and the ability to synthesize new myelin. Herein we review the main features of the regulatory aspect of these molecules based on recent findings and propose new putative signal molecules involved in the remyelination process, focused in the etiology of Multiple Sclerosis, one of the main demyelinating diseases causing disabilities in the population.

Cultured olfactory interneurons from Limax maximus: optical and electrophysiological studies of transmitter-evoked responses

1993 ◽  
Vol 69 (6) ◽  
pp. 1940-1947 ◽  
Author(s):  
L. D. Rhines ◽  
P. G. Sokolove ◽  
J. Flores ◽  
D. W. Tank ◽  
A. Gelperin
Keyword(s):  
Action Potential ◽  
Intracellular Calcium ◽  
Local Field ◽  
Local Field Potential ◽  
Field Potential ◽  
Optical Measurements ◽  
Optical Studies ◽  
Isolated Cells ◽  
Fura 2 ◽  
Limax Maximus

1. The olfactory processing network in the procerebral (PC) lobe of the terrestrial mollusk Limax maximus exhibits a coherent oscillation of local field potential that is modulated by odor input. To understand the cellular basis of this oscillation, we developed a cell culture preparation of isolated PC neurons and studied the responses of isolated cells to stimulation with neurotransmitters known to be present in the PC lobe. 2. The distribution of PC soma diameters suggests at least two different populations of neurons. Approximately 95% of isolated cells had soma diameters of 7-8 microns, with the remaining cells having larger diameters (10-15 microns). 3. Extracellular measurements of action potentials and optical measurements of intracellular calcium concentrations in fura-2-loaded cells were made. Serotonin and dopamine excited PC neurons and promoted transitions from steady to bursty activity. Both amines elicited increases in intracellular calcium, presumably concomitant with the increase in action-potential frequency. 4. Glutamate suppressed action-potential firing and reduced intracellular calcium. This effect was seen most clearly when glutamate was applied to cells excited by high potassium medium. Quisqualate is an effective glutamate agonist in this system, whereas kainate is not. 5. Combined with anatomic and biochemical data and with studies of the effects of these neurotransmitters on the oscillating local field potential of the intact PC network, the data from isolated PC neurons are consistent with the hypothesis that dopamine and serotonin modulate network dynamics, whereas glutamate is involved in generating the basic oscillation of local field potential in the PC. 6. The optical studies of fura-2-loaded cells showed that several treatments that increase the rate of action-potential production lead to elevations in intracellular calcium. Optical studies of intracellular calcium may be useful for multisite measurements of activity in the intact, oscillating PC lobe network.

Calcium Dynamics and Compartmentalization in Leech Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 4430-4440 ◽  
Author(s):  
Sofija Andjelic ◽  
Vincent Torre
Keyword(s):  
Information Processing ◽  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Ccd Camera ◽  
Calcium Dynamics ◽  
Single Action ◽  
Single Action Potential ◽  
Calcium Indicator ◽  
Mechanosensory Neurons

Calcium dynamics in leech neurons were studied using a fast CCD camera. Fluorescence changes (Δ F/ F) of the membrane impermeable calcium indicator Oregon Green were measured. The dye was pressure injected into the soma of neurons under investigation. Δ F/ F caused by a single action potential (AP) in mechanosensory neurons had approximately the same amplitude and time course in the soma and in distal processes. By contrast, in other neurons such as the Anterior Pagoda neuron, the Annulus Erector motoneuron, the L motoneuron, and other motoneurons, APs evoked by passing depolarizing current in the soma produced much larger fluorescence changes in distal processes than in the soma. When APs were evoked by stimulating one distal axon through the root, Δ F/ F was large in all distal processes but very small in the soma. Our results show a clear compartmentalization of calcium dynamics in most leech neurons in which the soma does not give propagating action potentials. In such cells, the soma, while not excitable, can affect information processing by modulating the sites of origin and conduction of AP propagation in distal excitable processes.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

Outward current and repolarization in hypoxic rat myocardium

1983 ◽  
Vol 244 (3) ◽  
pp. H341-H350
Author(s):  
C. H. Conrad ◽  
R. G. Mark ◽  
O. H. Bing
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Iodoacetic Acid ◽  
Mechanical Activity ◽  
Potential Range ◽  
Papillary Muscles ◽  
Rat Myocardium ◽  
Cable Properties ◽  
Sucrose Gap

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.

A SIMPLE MODEL FOR INTERACTION OF VOLTAGE AND CALCIUM DYNAMICS IN VIRTUAL VENTRICULAR TISSUE

2003 ◽  
Vol 13 (12) ◽  
pp. 3873-3886
Author(s):  
O. V. ASLANIDI ◽  
A. V. HOLDEN
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Cell Model ◽  
Excitation Threshold ◽  
Calcium Dynamics ◽  
Variable Model ◽  
Ventricular Cell ◽  
Calcium Dependent ◽  
Intracellular Ca ◽  
A Site

A simple two-variable model is used to replace the formulation of calcium dynamics in the Luo–Rudy ventricular cell model. Virtual ventricular cell and tissue are developed and validated to reproduce restitution properties and calcium-dependent voltage patterns present in the original model. Basic interactions between the membrane potential and Ca 2+ dynamics in the virtual cell and a strand of the virtual tissue are studied. Intracellular calcium waves can be linked to both action potentials (APs) and delayed afterdepolarizations (DADs). An intracellular calcium wave propagating from the cell interior can induce an AP upon reaching the cell membrane. The voltage and the intracellular Ca 2+ patterns within the same cell can be highly desynchronized. In a one-dimensional strand of the virtual tissue calcium motion is driven by the AP propagation. However, calcium release can be induced upon certain conditions (e.g. Na + overload of the cells), which results in DADs propagating in the wake of AP. Such propagating DADs can reach the excitation threshold, generating a pair of extrasystolic APs. Collision of a propagating AP with a site of elevated intracellular Ca 2+ concentration does not affect the propagation under the normal conditions. Under Na + overload local elevation of the intracellular Ca 2+ leads to generation of an extrasystolic AP, which destroys the original propagating AP.

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