A mathematical model of evoked calcium dynamics in astrocytes (Handy et al 2017)

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Accession:189344
" ...Here we present a qualitative analysis of a recent mathematical model of astrocyte calcium responses. We show how the major response types are generated in the model as a result of the underlying bifurcation structure. By varying key channel parameters, mimicking blockers used by experimentalists, we manipulate this underlying bifurcation structure and predict how the distributions of responses can change. We find that store-operated calcium channels, plasma membrane bound channels with little activity during calcium transients, have a surprisingly strong effect, underscoring the importance of considering these channels in both experiments and mathematical settings. ..."
Reference:
1 . Handy G, Taheri M, White JA, Borisyuk A (2017) Mathematical investigation of IP3-dependent calcium dynamics in astrocytes. J Comput Neurosci 42:257-273 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Glia;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): Ca pump; I_SERCA; I Calcium;
Gap Junctions:
Receptor(s): IP3;
Gene(s):
Transmitter(s):
Simulation Environment: MATLAB; XPP;
Model Concept(s): Calcium dynamics; Oscillations; Bifurcation;
Implementer(s): Handy, Gregory [handy at math.utah.edu]; Taheri, Marsa ;
Search NeuronDB for information about:  IP3; I Calcium; I_SERCA; Ca pump;
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
% Copyright: Marsa Taheri and Gregory Handy, 2016
% This code was used to simulate the mathematical model of Astrocyte 
% IP3-dependent Ca responses in 2 papers submitted in Nov 2016.
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
% Example file that simulates a calcium transients with a 
% specified IP3 input and collects transient characteristics/type
% Uses default channel parameters, which are found in Official_Params file
% Included IP3 parameters reproduce the simulations found in Fig. 2 
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
clear;
clc;
close all;
addpath('./Supporting_Functions');

Official_Params_TH; % loads the default parameters

% uncomment the line of code to produce wanted response
% reproduces calcium transients in Fig. 2
% JCNS, DOI: 10.1007/s10827-017-0640-1
% Order of parameters: amp d_rise r_rise d_decay 179
ip3_params=[0.2, 10, 0.2, 97 ]; % single-peak
%ip3_params=[0.26 41 0.12 200]; % multi-peak 
%ip3_params=[0.375, 34, 0.002, 138]; % plateau
%ip3_params=[0.55, 39, 0.002, 179]; % long-lasting

% overwrites the IP3 global variables to the chosen values
Amp = ip3_params(1);
d_rise = ip3_params(2);
r_rise = ip3_params(3);
d_decay = ip3_params(4);

% sets the simulation time 
dt = 0.01;
sim_t = [0:dt:120];

% finds the IP3 transient
IP3 = ip_function_TH(d_rise, d_decay, r_rise, Amp, stim_time, sim_t);

% the simulation begins at steady state (based on default parameter values)
init_cond=[0.0865415 36.49084 0.6255124];

% runs the simulation using ode45
options = odeset('AbsTol', 10^-6, 'RelTol', 10^-6, 'MaxStep', 0.1);
[sim_t,ca_transient] = ode15s(@Paper_Ca_ODE_TH, sim_t, init_cond, options);
% saves the calcium transient

CaCyt = ca_transient(:,1);
CaT =  ca_transient(:,2);
h =  ca_transient(:,3);

%% Plots the calcium transient and outputs response type 
[TrueTroughVal, TrueTroughLoc, PeakVal,PeakLoc]=plotCa_TH(CaCyt,...
    sim_t, 'time');
set(gca,'fontsize',16)
axis([0 max(sim_t) 0 max(CaCyt)])
xlabel('Time (sec)','fontsize',16)
ylabel('[Ca] (\muM)','fontsize',16)

%Prints the calcium response type
[Result, CaDur, CaAmount, CaLatency, StartOfResp,EndOfResp]=...
    FourCaResponseTypes_TH(TrueTroughVal,TrueTroughLoc, PeakVal,...
    PeakLoc, CaCyt, sim_t, 20);

%% Data collection and plot

% Stores characteristics about the IP3 transient
[IP3Amount, IP3PkLoc, IP3Amp, IP3TrueDur] = IP3Dyn_model_TH(IP3,sim_t);

% Stores characteristics about the Calcium transient
CaIP3PeakLatency=PeakLatency_TH(CaCyt, IP3);

CaAmp = max(PeakVal);

if strcmp(Result, 'NR')==0
    [CaRiseTime, CaDecTime] = CaRiseAndDecay_TH(CaCyt, dt);
else
    CaRiseTime=0; CaDecTime=0; CaAmp=0;
end

%Collects and saves information regarding the calcium and IP3 transients 
AllResults1=[d_decay, d_rise, r_rise, IP3Amp, IP3Amount,IP3TrueDur,...
    CaAmp, CaAmount, CaDur, CaLatency, CaRiseTime, CaDecTime];
AllResults2=[Result, CaIP3PeakLatency];

clearvars -except AllResults1 AllResults2


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