function [Y,T_run] = FoxLu_StoHH(t, Ifunc, Area,seed)
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% by Shusen Pu
%%% Outputs
% Y(:,1) : t
% Y(:,2) : V
% Y(:,3) : fraction open Na channels
% Y(:,4) : fraction open K channels
% Y(:,5) : m
% Y(:,6) : h
% Y(:,7) : n
rng(seed)
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% Initialize quantities needed to run solver
t_ind=tic;
% time step size
dt = t(2)-t(1);
% Number of time steps
nt = length(t); % total
nt1 = nt-1; % at which to solve
% Initial Values
t0 = t(1);
V0 = 0;
m0 = alpham(V0) / (alpham(V0) + betam(V0)); % m
h0 = alphah(V0) / (alphah(V0) + betah(V0)); % h
n0 = alphan(V0) / (alphan(V0) + betan(V0)); % n
% Initialize Output
Y = zeros(nt,4);
Y(1,1) = V0;
Y(1,2) = m0;
Y(1,3) = h0;
Y(1,4) = n0;
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% Parameter Values
% Number of Channels
NNa = round(Area*60); % Na
NK = round(Area*18); % K
% Capacitance
C = 1; % muF /cm^2
% Na Current
gNa = 120; % mS/cm^2
ENa = 120; % mV
% K Current
gK = 36; % mS/cm^2
EK = -12; % mV
% Passive Leak
gL = 0.3; % mS / cm^2
EL = 10.6; % mV
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% Determine Which Noise Model and Do Some Necessary Setup
mNoiseVec = randn(nt1,1);
% Imposing bounds on argument of sqrt functions, not directly altering dynamics of the subunits
% mNoise = @(V,m,i) sqrt((alpham(V)*(1-m) + betam(V)*m)/NNa) * mNoiseVec(i-1);
mNoise = @(V,m,i) sqrt(2)*sqrt((alpham(V)*(1-m) + betam(V)*m)/NNa) * mNoiseVec(i-1);
hNoiseVec = randn(nt1,1);
%hNoise = @(V,h,i) sqrt((alphah(V)*(1-h) + betah(V)*h)/NNa) * hNoiseVec(i-1);
hNoise = @(V,h,i) sqrt(2)*sqrt((alphah(V)*(1-h) + betah(V)*h)/NNa) * hNoiseVec(i-1);
nNoiseVec = randn(nt1,1);
% nNoise = @(V,n,i) sqrt((alphan(V)*(1-n) + betan(V)*n)/NK) * nNoiseVec(i-1);
nNoise = @(V,n,i) sqrt(2)*sqrt((alphan(V)*(1-n) + betan(V)*n)/NK) * nNoiseVec(i-1);
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%%%%%% HERE IS THE SOLVER %%%%%%%%%%%%%%%%%%%%%%%
%%%%%% USING EULER FOR ODEs, %%%%%%%%%%%%%%%%%%%%%%%
%%%%%% EULER-MARUYAMA FOR SDEs, and %%%%%%%%%%%%%%%%%%%%%%%
%%%%%% GILLESPIE FOR MARKOV CHAIN %%%%%%%%%%%%%%%%%%%%%%%
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for i=2:nt
% Input Current
I = Ifunc(t(i-1));
% Update subunits
% Noise terms are non-zero for Subunit Noise model
m = m0 + dt*(alpham(V0)*(1-m0) - betam(V0)*m0) + mNoise(V0,m0,i)*sqrt(dt); % shifted to i-1 in function
h = h0 + dt*(alphah(V0)*(1-h0) - betah(V0)*h0) + hNoise(V0,h0,i)*sqrt(dt);
n = n0 + dt*(alphan(V0)*(1-n0) - betan(V0)*n0) + nNoise(V0,n0,i)*sqrt(dt);
% skip that method (from Fox and Lu 1994 )
while (m-1)*(m-0)>0
m = m0 + dt*(alpham(V0)*(1-m0) - betam(V0)*m0) + sqrt(2)*sqrt((alpham(V)*(1-m) + betam(V)*m)/NNa) * randn*sqrt(dt);
end
while (h-1)*(h-0)>0
h = h0 + dt*(alphah(V0)*(1-h0) - betah(V0)*h0) + sqrt(2)*sqrt((alphah(V)*(1-h) + betah(V)*h)/NNa) * randn*sqrt(dt);
end
while (n-1)*(n-0)>0
n = n0 + dt*(alphan(V0)*(1-n0) - betan(V0)*n0) + sqrt(2)*sqrt((alphan(V)*(1-n) + betan(V)*n)/NK) * randn*sqrt(dt);
disp('n goes out of bounds')
end
% Enforce boundary conditions (only necessary for subunit noise model
% m = max(0,min(1,m));
% h = max(0,min(1,h));
% n = max(0,min(1,n));
% Note: Impose bounds on fractions to avoid <0 or >1 in dV/dt equation, this doesn't directly alter the dynamics of the subunits or channels
NaFraction = m0^3*h0; % Fluctuations are non-zero for Conductance Noise Models
KFraction = n0^4;
% Update Voltage
Vrhs = (-gNa*(NaFraction)*(V0 - ENa)-gK*(KFraction)*(V0 - EK) - gL*(V0-EL) + I)/C;
V = V0 + dt*Vrhs ; % VNoise is non-zero for Current Noise Model
% Save Outputs
Y(i,1) = V;
Y(i,2) = m;
Y(i,3) = h;
Y(i,4) = n;
% Keep "old values" to use in next Euler time step
V0 = V;
m0 = m;
h0 = h;
n0 = n;
end % End loop over time for SDE solver
T_run=toc(t_ind);
end % End Function Definition
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%%%%%% END OF SOLVER %%%%%%%%%%%%%%%%%%%%%%%
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% Define functions used above
% subunit kinetics (Hodgkin and Huxley parameters)
function out = alpham(V)
out = 0.1 * (25-V)/ (exp((25-V)/10)-1);
end
function out = betam(V)
out = 4 * exp(-V/18);
end
function out = alphah(V)
out = 0.07 * exp(-V/20);
end
function out = betah(V)
out = 1/ (exp((30-V)/10)+1);
end
function out = alphan(V)
out = 0.01 * (10-V) / (exp((10-V)/10)-1);
end
function out = betan(V)
out = 0.125 * exp(-V/80);
end