Consequences of HERG mutations in the long QT syndrome (Clancy, Rudy 2001)

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Accession:58172
This study demonstrates which mutations can prolong APD sufficiently to generate early afterdepolarizations (EADs), which may trigger life-threatening arrhythmias. The severity of the phenotype is shown to depend on the specific kinetic changes and how they affect I(Kr) during the time course of the action potential. See paper for more and details.
Reference:
1 . Clancy CE, Rudy Y (2001) Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death. Cardiovasc Res 50:301-13 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Heart cell;
Channel(s): I K; I_HERG;
Gap Junctions:
Receptor(s):
Gene(s): HERG KCNH2;
Transmitter(s):
Simulation Environment: XPP;
Model Concept(s): Ion Channel Kinetics; Heart disease; Long-QT;
Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]; Chang, Han-Dong; Wu, Jiun-Shian [coolneon at gmail.com];
Search NeuronDB for information about:  I K; I_HERG;
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clancyrudy2001
readme.html
ierg_mar.jpg
IERG_Mar.ode
                            
% Markovian model for wild-type cardiac KERG K+ current.  Written by Dr. Sheng-Nan Wu, Han-Dong Chang and Jiun-Shian Wu
%Clancy CE and Rudy Y. Cellular consequences of HERG mutations in the long QT syndrome:
% precursors to sudden cardiac death. Cardiovasc Res 2001;50:301-313.
% Simulations (i.e., macroscopic erg current) can reproduce the result shown at Fig. 4B in this paper.

% Constants
R=8.314
F=96.485
Temp=310

% Initial values
ini c3=1
ini c2=0
ini c1=0
ini o=0.06
ini i=0

% Values of the model parameters
par ko=5.4
par ki=140
par vhold=-40, vtest=0
par ton=50, toff=300
v=vhold+heav(t-ton)*heav(toff-t)*(vtest-vhold)

% Activation  functions
vk=((R*Temp)/F)*ln(ko/ki)
Gk=1.35e-2*ko^0.59
a=5.55e-2* exp(0.05547153*(v-12)) 
b=2.357e-3* exp(-0.036588*(v))
ain=2.172
bin=1.077
aa=6.55e-2* exp(0.05547153*(v-36))
bb=2.9357e-3* exp(-0.02158*(v))
ai=0.439*exp(-0.02352*(v+25))*4.5/ko
bi=0.656*exp(0.000942*(v))*(4.5/ko)^0.3 
u=(ai*bb*aa)/(aa*bin)

% Gating functions
dc3/dt=b*c2-a*c3
dc2/dt=bin*c1+a*c3-(ain+b)*c2
dc1/dt=ain*c2+bb*o+u*i-(bin+2*aa)*c1
do/dt=ai*i+aa*c1-(bi+bb)*o
di/dt=aa*c1+bi*o-(u+ai)*i

aux ik=Gk*o*(v-vk)

% Numerical and plotting parameters for xpp
@ meth=Euler, dt=.1, total=800
@ yp=ik, yhi=1.0, ylo=-0.1, xlo=0, xhi=800, bound=100
done

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