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Alternating Electromagnetic Field To Affect The Mechanism Of Cytoplasmic Calcium

Posted on:2010-06-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:M Y LuoFull Text:PDF
GTID:1110360302457508Subject:Biophysics
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Interest in hazardous consequences of so-called 'electromagnetic pollution' is increasing within the scientific community. In recent years, researches on biological effects of eletromagnetic filed focus on two aspects: epidemiological investigation and experimental study of cell. In this paper, we take the second messenger calium ion in the cell for the study. The dynamic models on the calcium concentration in the cytosol [Ca2+]cyt was built for single cell. Models include the cellular physiology and changes of the action potential (Vm) of the plasma membrane. A novel thought to explain the mechanism for alternating eletromagnetic filed induced-effects on cytosolic calcium was put forward. The main conclusions were:(1) The sensitivity of calcium channels on the plasma membrane and calcium stores is discussed for the calcium nonlinear dynamic in the cytosol based on the 'minimal model' about calcium oscillation. The simulated result shows that the ATP-pump on the calcium store is the most sensitive part in the model. This result is consistent with some empirical literatures. The ATP-pump is the possible active part of the eletromagnetic field.(2) Vm-[Ca2+]cyt modelThe Vm-[Ca2+]cyt model includes all channels in the plasma involving in the changes of [Ca2+]cyt.①The mechanism for the alternating electric field induced-effects on Vm and [Ca2+]cyt was elucidated. An alternating external electric field may exert an oscillating force (F1=Ezqe=E0zqe sin(2πvt)) to each of the free electrolytes, existing on both sides of the plasma membrane. When the force gets to a special value, some membrane proteins will open or close. Thus the changes of the membrane potential will impact the influx and outflux of ions. Consequently, the [Ca2+]cyt changes. The simulated results showed a correlation between the changes of [Ca2+]cyt and the alternating electric field. When the numerical ratio between the intensity E0 (mV/m) and the frequency v (Hz) of the field was about 1~2, the [Ca2+]cyt signal was changed dramatically. The bioactive changes of [Ca2+]cyt appeared at low frequency, at the range of 0~100Hz.②An alternating external magnetic field may exert an oscillating force (F1=Buzqe=B0uzqe sin(2πvt)) to each of the free electrolytes. In the same way, when the numerical ratio between the intensity B0 (G) and the frequency v (Hz) of the field was about B0 > 4v, the [Ca2+]cyt signal was changed dramatically.(3) Vm-[Ca2+]cyt-[Ca2+]ER modelThe Vm-[Ca2+]cyt-[Ca2+]ER model includes not only the channels in the plasma membrane, but also the membrane of endoplasmic reticulum (ER).From the simulated results, we can concluded when the calcium fluxes in the ER is considered, the reaction frequency of the electromagnetic on the [Ca2+]cyt is enlarged dramatically. It proved that the possible active part located on the calcium stores.Besides the paper have docked integrinαⅡbβ3 and the RGD sequence. IntegrinαⅡbβ3 of the platelet surfaces regulates the thrombosis formation.αⅡbβ3 binds to the RGD sequence (Arg-Gly-Asp) of fibrinogen, promotes the platelet aggregation and finally leads to the thrombus. We obtained the three-dimensional molecular structure ofαⅡbβ3 using homology-modeling (modeller8v2 software), with integrinαvβ3 (pdb code 1JV2) as the template. Accordingly, a cyclic RGD(RGD-c) peptide was designed to bindαⅡbβ3 as an antagonist and to block the formation of thrombus. We added two amino acids X, Y to both sides of RGD. X and Y could bind to each other by disulfide bond that finally made RGD-c cyclic peptide. The optimum structure of RGD-c was obtained from the energetic optimization processes. All amino acids were placed at the X and Y to conduct molecular docking to the integrinαⅡbβ3 We got the optimum structure of RGD-c by energetic optimization and the antagonistic combination analysis. The results might provide an insight into designing and screening integrinαⅡbβ3 antagonists.
Keywords/Search Tags:Alternating electromagnetic field, Calcium ion, Calcium oscillation Transmembrane action potential, Homology simulation, Docking
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