MODELING EFFECT OF SODIUM PUMP ON CALCIUM OSCILLATIONS IN NEURON CELLS

2012 ◽  
Vol 04 (03) ◽  
pp. 1250010 ◽  
Author(s):  
SHIVENDRA G. TEWARI ◽  
K. R. PARDASANI

Calcium plays a significant role in a number of processes like muscle contraction, gene expression, synaptic plasticity, signal transduction etc. but the significance of calcium oscillation is not yet completely understood in most of the cell types. A number of investigators have reported the oscillatory behavior of calcium due to intracellular concentration of inositol 1,4,5-trisphosphate (IP3). In this paper, an attempt has been made to study the oscillations induced in calcium due to dynamically changing membrane potential with special relevance to sodium pump. A mathematical model is developed which incorporates nearly all important and necessary biophysical components like L-type calcium channel, sodium channel, potassium channel, cytosolic buffers, calcium pump, sodium–calcium exchanger (NCX), sodium–potassium ATPase (sodium pump), and dynamic membrane potential. These channels have realistic gating mechanism and emulate the gating mechanism proposed in the famous paper of Hodgkin and Huxley.1 The model leads to an initial value problem involving system of non-linear ordinary differential equations. A numerical solution has been obtained using Gear's method. The numerical results have been used to study the effect of sodium pump over the frequency of Ca 2+ oscillation. At lower and higher sodium pump current densities the Ca 2+ oscillation frequency is observed to be 278 Hz and 225 Hz respectively.

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yoothana Suansook ◽  
Kitti Paithoonwattanakij

The calcium oscillations have many important roles to perform many specific functions ranging from fertilization to cell death. The oscillation mechanisms have been observed in many cell types including cardiac cells, oocytes, and hepatocytes. There are many mathematical models proposed to describe the oscillatory changes of cytosolic calcium concentration in cytosol. Many experiments were observed in various kinds of living cells. Most of the experimental data show simple periodic oscillations. In certain type of cell, there exists the complex periodic bursting behavior. In this paper, we have studied further the fractional chaotic behavior in calcium oscillations model based on experimental study of hepatocytes proposed by Kummer et al. Our aim is to explore fractional-order chaotic pattern in this oscillation model. Numerical calculation of bifurcation parameters is carried out using modified trapezoidal rule for fractional integral. Fractional-order phase space and time series at fractional order are present. Numerical results are characterizing the dynamical behavior at different fractional order. Chaotic behavior of the model can be analyzed from the bifurcation pattern.


1990 ◽  
Vol 259 (3) ◽  
pp. C402-C408 ◽  
Author(s):  
E. P. Burke ◽  
K. M. Sanders

Previous studies have suggested that the membrane potential gradient across the circular muscle layer of the canine proximal colon is due to a gradient in the contribution of the Na(+)-K(+)-ATPase. Cells at the submucosal border generate approximately 35 mV of pump potential, whereas at the myenteric border the pump contributes very little to resting potential. Results from experiments in intact muscles in which the pump is blocked are somewhat difficult to interpret because of possible effects of pump inhibitors on membrane conductances. Therefore, we studied isolated colonic myocytes to test the effects of ouabain on passive membrane properties and voltage-dependent currents. Ouabain (10(-5) M) depolarized cells and decreased input resistance from 0.487 +/- 0.060 to 0.292 +/- 0.040 G omega. The decrease in resistance was attributed to an increase in K+ conductance. Studies were also performed to measure the ouabain-dependent current. At 37 degrees C, in cells dialyzed with 19 mM intracellular Na+ concentration [( Na+]i), ouabain caused an inward current averaging 71.06 +/- 7.49 pA, which was attributed to blockade of pump current. At 24 degrees C or in cells dialyzed with low [Na+]i (11 mM), ouabain caused little change in holding current. With the input resistance of colonic cells, pump current appears capable of generating at least 35 mV. Thus an electrogenic Na+ pump could contribute significantly to membrane potential.


1997 ◽  
Vol 63 (2-3) ◽  
pp. 221-239 ◽  
Author(s):  
Marko Marhl ◽  
Stefan Schuster ◽  
Milan Brumen ◽  
Reinhart Heinrich

1981 ◽  
Vol 1 (1) ◽  
pp. 1-8 ◽  
Author(s):  
M L Pall ◽  
J M Trevillyan ◽  
N Hinman

Strains of Neurospora crassa mutant in either of two genes, Crisp-1 (cr1) and Frost (fr), showed no increase of cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels when subjected to several treatments which produce large increases of cyclic AMP in wild-type Neurospora. Evidently, the previously reported deficiencies of adenylate cyclase in these mutants were sufficient to block the normal increases. This fact suggests that both mutants could be used to help determine which control phenomena involve cyclic AMP and to interrupt the control of established cyclic AMP-regulated functions. Earlier studies had suggested an interdependence of the cyclic AMP level and the electric potential difference across the plasma membrane of Neurospora. Present experiments, therefore, employed several strains with the cr1 mutation to test for possible roles of cyclic AMP in recovery and oscillatory behavior of the Neurospora membrane potential. The results showed all such phenomena to be normal in the adenylate cyclase-defective strains, which demonstrates that variations of cyclic AMP are not obligatorily involved in the apparent control processes. Evidence is also presented that the induction of both glucose transport system II and the alternative oxidase do not require elevated cyclic AMP levels.


1978 ◽  
Vol 235 (1) ◽  
pp. C63-C68 ◽  
Author(s):  
R. F. Abercrombie ◽  
P. de Weer

The operation of the sodium pump of giant axons of the squid, Loligo pealei, has been studied simultaneously in two independent ways: 1) by measuring sodium efflux with 22Na, and 2) by calculating the transmembrane current generated by the pump from measurements of membrane resistance and digitalis-sensitive membrane potential. In normal, untreated axons, the effect of increasing the external potassium concentration on both sodium efflux and pump current is similar, which suggests that Na:K pump stoichiometry remains relatively constant in the range of 0-20 mM external K. The data are compatible with a 3:2 Na:K ratio. In axons whose intracellular ADP level has been elevated by injection of L-arginine, a large, electrically silent, cardiotonic steroid-sensitive sodium efflux takes place in the absence of external potassium; this suggests that pump-mediated Na:Na exchange is 1:1 or electroneutral. Finally, elevation of external potassium levels causes the appearance, in high-ADP axons, of electrogenic pumping, with little effect on sodium efflux; hence, in contrast to what is seen in normal (low-ADP) axons, the charge translocated, per sodium ion extruded, increases sharply with increasing extracellular potassium levels.


2019 ◽  
Vol 31 (6) ◽  
pp. 1066-1084 ◽  
Author(s):  
Henri Hokkanen ◽  
Vafa Andalibi ◽  
Simo Vanni

Recently, Markram et al. (2015) presented a model of the rat somatosensory microcircuit (Markram model). Their model is high in anatomical and physiological detail, and its simulation requires supercomputers. The lack of neuroinformatics and computing power is an obstacle for using a similar approach to build models of other cortical areas or larger cortical systems. Simplified neuron models offer an attractive alternative to high-fidelity Hodgkin-Huxley-type neuron models, but their validity in modeling cortical circuits is unclear. We simplified the Markram model to a network of exponential integrate-and-fire (EIF) neurons that runs on a single CPU core in reasonable time. We analyzed the electrophysiology and the morphology of the Markram model neurons with eFel and NeuroM tools, provided by the Blue Brain Project. We then constructed neurons with few compartments and averaged parameters from the reference model. We used the CxSystem simulation framework to explore the role of short-term plasticity and GABA[Formula: see text] and NMDA synaptic conductances in replicating oscillatory phenomena in the Markram model. We show that having a slow inhibitory synaptic conductance (GABA[Formula: see text] allows replication of oscillatory behavior in the high-calcium state. Furthermore, we show that qualitatively similar dynamics are seen even with a reduced number of cell types (from 55 to 17 types). This reduction halved the computation time. Our results suggest that qualitative dynamics of cortical microcircuits can be studied using limited neuroinformatics and computing resources supporting parameter exploration and simulation of cortical systems. The simplification procedure can easily be adapted to studying other microcircuits for which sparse electrophysiological and morphological data are available.


2000 ◽  
Vol 116 (1) ◽  
pp. 47-60 ◽  
Author(s):  
R. Daniel Peluffo ◽  
José M. Argüello ◽  
Joshua R. Berlin

The roles of Ser775 and Glu779, two amino acids in the putative fifth transmembrane segment of the Na,K -ATPase α subunit, in determining the voltage and extracellular K + (K +o) dependence of enzyme-mediated ion transport, were examined in this study. HeLa cells expressing the α1 subunit of sheep Na,K -ATPase were voltage clamped via patch electrodes containing solutions with 115 mM Na+ (37°C). Na,K -pump current produced by the ouabain-resistant control enzyme (RD), containing amino acid substitutions Gln111Arg and Asn122Asp, displayed a membrane potential and K +o dependence similar to wild-type Na,K -ATPase during superfusion with 0 and 148 mM Na+-containing salt solutions. Additional substitution of alanine at Ser775 or Glu779 produced 155- and 15-fold increases, respectively, in the K +o concentration that half-maximally activated Na,K -pump current at 0 mV in extracellular Na+-free solutions. However, the voltage dependence of Na,K -pump current was unchanged in RD and alanine-substituted enzymes. Thus, large changes in apparent K +o affinity could be produced by mutations in the fifth transmembrane segment of the Na,K -ATPase with little effect on voltage-dependent properties of K + transport. One interpretation of these results is that protein structures responsible for the kinetics of K +o binding and/or occlusion may be distinct, at least in part, from those that are responsible for the voltage dependence of K +o binding to the Na,K -ATPase.


2016 ◽  
Vol 11 (12) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
Nino Sharikadze ◽  
Natia Jojua ◽  
Maia Sepashvili ◽  
Elene Zhuravliova ◽  
David G Mikeladze

Nobiletin is an O-methylated flavonoid found in citrus peels that have anticancer, antiviral, neuroprotective, anti-inflammatory activities and depending on the cell types exhibits both pro- or anti-apoptotic properties. We have found that nobiletin decreases oxygen consumption by bovine brain isolated mitochondria in the presence of glutamate and malate and increases in the presence of succinate. In parallel, nobiletin increases NADH oxidation, a-ketoglutarate dehydrogenase activities and through matrix substrate-level phosphorylation elevates the a-ketoglutarate-dependent production of ATP. In addition, nobiletin reduces the production of peroxides in the presence of complex I substrates and slightly enhances succinate-driven H2O2 formation. Besides, nobiletin induces transient elevation of membrane potential followed by mild depolarization. Affinity purified nobiletin binding proteins revealed one major anti-NDUFV1 positive protein with 52kD and NADH: ubiquinone oxidoreductase activity. This fraction can produce peroxide that is inhibited by nobiletin. We propose that nobiletin may act as a mild “uncoupler”, which through activation of a-ketoglutarate dehydrogenase (a-KGDH)-complex and acceleration of matrix substrate-level phosphorylation maintains membrane potential at an abnormal level. This switch in mitochondrial metabolism could elevate succinate-driven oxygen consumption that may underlay in both pro- and anti-apoptotic effects of nobiletin.


Physiology ◽  
2000 ◽  
Vol 15 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Jean-Pierre Savineau ◽  
Roger Marthan

In a variety of smooth muscle cells, agonists activating membrane receptors induce oscillations in the cytoplasmic Ca2+ concentration via an inositol trisphosphate-activated mechanism. Ca2+ oscillations participate in the control of cell membrane potential and the tone of smooth muscle. There is evidence that alterations in Ca2+ oscillations modulate smooth muscle responsiveness.


Sign in / Sign up

Export Citation Format

Share Document