November 23, 2010

UNIVERSITY OF RHODE ISLAND

Department of Electrical, Computer and Biomedical Engineering

BME 307 Bioelectricity Fall 2010

McAllister-Noble-Tsien Model of the Purkinje Action Potential

Simulation Project
Report due on Tuesday, December 21, 2010, by 3 pm

The Matlab scripts and functions you wrote as part of Homework 8 and 9 are the starting point. You will modify
your scripts and/or functions, and possibly create new ones, to conduct this experiment and analyze the results.

Report: Your report should be targeted to an audience that understands the Hodgkin-Huxley model, but not your
topic of study. The report must include a statement of the problem (or the question being studied), the methods
used to solve the problem (including equations and numerical algorithms), and the results of your investigation.
Figures or graphics may be integrated with the text or arranged sequentially immediately after the references. The
report must close with a discussion section, where the results and their implications are described. Plots must show
appropriately labeled axes, including units. Appendices will contain your scripts and any lengthy derivations. Full
citations to any reference materials used in your study must be included.

Score: The projects will be graded 15% for your analysis (the content of the report) and 5% for the style of the
report. Superior reports will include analysis beyond what is required.

The McAllister-Noble-Tsien (MNT) model [1] simulates the action potential in cardiac Purkinje fibers.
This model has provided a wealth of information on the electrical conduction system in the heart [2, 3, 4].
The formulation follows that of the Hodgkin-Huxley model: nonlinear membrane conductances are
modeled using a saturation value and activation or inactivation gates, with voltage-dependent opening
and closing rates. This model is more complex, however, because it reproduces the natural rhythmic
depolarizations of the Purkinje fiber. In addition, two currents describe potassium efflux during
repolarization, and the model includes two chloride currents.

The purpose of this study is to implement the MNT model and compare the Purkinje action potential to
the action potential in the squid giant axon.

The MNT model uses ten state variables:

1. Vm , membrane potential 6. q, chloride inactivation gate

2. m, sodium activation gate 7. r, chloride inactivation gate

3. h, sodium inactivation gate 8. s, potassium pacemaker gate

4. d, slow sodium activation gate 9. x1 , plateau potassium gate

5. f , slow sodium inactivation gate 10. x2 , another plateau potassium gate

These state variables are handled much the same way as those in the Hodgkin-Huxley model. The
complete MNT model is listed below. The simulation will generate a membrane action potential (a
non-propagating action potential at a point).

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 BME 307 November 23, 2010

Modify the Hodgkin-Huxley scripts to implement the MNT Purkinje fiber model. The simulation should
cover 4 seconds using a time step ∆t = 0.01 milliseconds.

Show the parallel conductance model of the MNT membrane. Generate plots of the membrane potential,
currents, gates and their time constants. Compute the action potential duration at 90% repolarization
(APD90 ) and the maximum upstroke velocity, dVm /dtmax . What is the intrinsic firing rate of the model
cell? How does the action potential change shape in a chloride-free preparation? Does APD90 or
dVm /dtmax change? You should read the original article [1] and one with corrections [2] for more
information.

McAllister-Noble-Tsien Model of the Purkinje Action Potential

Currents are given in µA/cm2 , conductances in mS/cm2 , and potentials in mV. Note that l’Hôpital’s rule
must be applied to the last term of JK1 in addition to some opening rates.

Jion = JN a + Jsi + JK1 + JK2 + Jx1 + Jx2 + Jqr + JN a,b + JCl,b ion current
JN a = g N a · m3 · h · (Vm − EN a ) fast Na+ current
Jsi = (g si · d · f + g 0si · d0 ) · (Vm − Esi ) secondary inward current
where d0 = 1/ {1 + exp [−0.15 (Vm + 40)]}
Jqr = g qr · q · r · (Vm − ECl ) transient Cl− current

JK2 = s · K2
K2 = 2.8 {exp [0.04(Vm + 110)] − 1} / {exp [0.08(Vm + 60)] + exp [0.04(Vm + 60)]}
pacemaker K+ current
JK1 = K2 /2.8 + 0.2 (Vm + 30) / {1 − exp [−0.04(Vm + 30)]} background K+ current
Jx1 = x1 · 1.2 {exp [0.04 (Vm + 95)] − 1} /exp [0.04(Vm + 45)]
nonlinear plateau K+ current
Jx2 = x2 · (25 + 0.385 Vm ) linear plateau K+ current
JN a,b = 0.105 (Vm − EN a ) background Na+ current
JCl,b = 0.01 (Vm − ECl ) background Cl− current

Nernst potentials, conductances, and membrane capacitance:

EN a = 40 gN a = 150
ECl = −70 g si = 0.8
Esi = 70 g 0si = 0.04
Cm = 10 µF/cm2 g qr = 2.5

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 BME 307 November 23, 2010

The initial values of the state variables are:

Vm = −80 mV q = 2.156 × 10−6
m = 0.01946 r = 0.1190
h = 0.85910 s = 0.7791
d = 0.002089 x1 = 0.02694
f = 0.7725 x2 = 0.01986

The nine gates are governed by the opening and closing rates (in msec−1 ):

Vm + 47
αm = βm = 40 exp [−(Vm + 72)/17.86]
1 − exp [−(Vm + 47)/10]
2.5
αh = 0.0085 exp [−(Vm + 71)/5.43] βh =
1 + exp [−(Vm + 10)/12.2]

0.002 (Vm + 40)

αd = βd = 0.02 exp [−(Vm + 40)/11.26]
1 − exp [−(Vm + 40)/10]
0.02
αf = 0.000987 exp [−0.04(Vm + 60)] βf =
1 + exp [−(Vm + 26)/11.49]

0.008Vm
αq = βq = 0.08 exp [−Vm /11.26]
1 − exp [−Vm /10]
0.02
αr = 0.00018 exp [−(Vm + 80)/25] βr =
1 + exp [−0.087(Vm + 26)]

0.001 (Vm + 52)

αs = βs = 5.0 × 10−5 exp [−(Vm + 52)/14.93]
1 − exp [−(Vm + 52)/5]

0.0005 exp [(Vm + 50)/12.1] 0.0013 exp [−(Vm + 20)/16.67]

αx1 = βx1 =
1 + exp [(Vm + 50)/17.5] 1 + exp [−(Vm + 20)/25]

1.27 × 10−4 0.0003 exp [−(Vm + 20)/16.67]

αx2 = βx2 =
1 + exp [−(Vm + 19)/5] 1 + exp [−(Vm + 20)/25]

[1] R. E. McAllister, D. Noble, and R. W. Tsien. Reconstruction of the electrical activity of cardiac
Purkinje fibres. J Physiol, 251(1):1–59, Sep 1975.
[2] M. R. Guevara and A. Shrier. Phase resetting in a model of cardiac Purkinje fiber. Biophys J,
52(2):165–175, Aug 1987.
[3] D. R. Chialvo, D. C. Michaels, and J. Jalife. Supernormal excitability as a mechanism of chaotic
dynamics of activation in cardiac Purkinje fibers. Circ Res, 66(2):525–545, Feb 1990.
[4] T. R. Chay and Y. S. Lee. Impulse responses of automaticity in the Purkinje fiber. Biophys J,
45(4):841–849, Apr 1984.

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