A MODEL OF THE RAT PHRENIC MOTOR
NEURON B. Amini1 , A.
Bidani2, J.B. Zwischenberger3, J.W. Clark,
Jr.4
1Department of Neurobiology and Anatomy,
University of Texas Health Science Center at Houston, Houston, TX,
USA 2Department of Internal Medicine, University of
Texas Health Science Center at Houston, Houston, TX, USA
3Department of Surgery, University of Texas Medical
Branch, Galveston, TX, USA 4Department of Electrical
and Computer Engineering, Rice University, Houston, TX, USA
Abstract We have developed a model for the
rat phrenic motor neuron (PMN) that robustly replicates many
experimentally observed behaviors of PMNs in response to
pharmacological, ionic, and electrical perturbations using a single
set of parameters. Our model suggests that the after-depolarization
(ADP) response seen in action potentials is a result of the slow
deactivation of the fast sodium channel in the range of the ADP
coupled with the activation of the L-type calcium channel
(ICaL). This current and its interactions with the small
and large conductance calcium-activated potassium currents
(IKCaSK and IKCaBK, respectively) is also
important in the generation of spike frequency adaptation in the
repetitive firing mode of activity. Other aspects of the model
conform very well to experimental observations in both the action
potential and repetitive firing mode of activity, including the role
of IKCaSK in the medium after-hyperpolarization (AHP),
and the role of IKCaBK in the fast AHP. We have made a
number of predictions using the model, including the existence of
two putative sodium currents (fast and persistent), as well as,
functional roles for the N- and T-type calcium currents.
Computational Aspects Simulations were
performed on PCs running Linux and Windows XP and solved using a
5th order Runge-Kutta-Merson numerical integration
algorithm that includes an automatic step-size adjustment based on
error estimates. The tolerance for the integration was
0.5×10-6.
The equations were coded in the C language and compiled using the
GNU C-compiler and Microsoft Visual C++ (for Linux and Windows XP,
respectively). The executable (AApmn.exe) looks for a parameter file
(pmn_parsed.d) and an initial condition file (pmn_init_cond.d) in
the same directory. The parameters in pmn_parsed.d are in the
following order: simulation duration (ms), baseline injected current
(nA, for adjusting resting membrane potential), stimulation current
(nA), stimulation start time (ms), stimulation end time (ms),
followed by the maximal conductances for INa,
ICaL, IK, IA, ID,
IR, IBNa, IBCa, INaK,
ICaP, INaCa, IKCaSK,
IKCaBK, and INaP.
The simulation output is written to a text file (pmn_result.dat).
Each row of this file has time as the first column followed by
membrane potential, intracellular calcium, INa,
ICaL, IK, IA, ID,
IR, IBNa, IBCa, INaK,
ICaP, INaCa, IKCaSK,
IKCaBK, INaP, and Itotal. A Matlab
(MathWorks, Natick, MA) M-file (ReadResults.m) reads the output file
and assigns variable names to the coulmns.
Files to Download The aforementioned
files can be downloaded as a tar.gz archive, pmn.tar.gz (8
KB). A separate archive, pmnMS.zip (46
KB), is presented for the convenience of Microsoft Visual C++ users.
Microsoft windows users without access to Visual C++ can run the
executable (AApmn.exe) found in the Release directory (see below).
This directory also contains the initial condition and parameter
files needed by the program.
The archive contents are shown below.
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pmn.tar.gz |
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pmn |
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makefile |
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pmn_current.c |
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pmn_deriv.c |
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pmn_driver.c |
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pmn_reader.c |
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pmn_runge_kutta.c |
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pmn_subs.h |
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pmn_init_cond.d |
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pmn_parsed.d |
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ReadResults.m |
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pmnMS.zip |
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pmnMS |
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Release |
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AApmn.exe |
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pmn_init_cond.d |
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pmn_parsed.d |
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ReadResults.m |
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AApmn.dsp |
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AApmn.dsw |
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AApmn.ncb |
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AApmn.opt |
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AApmn.plg |
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pmn_current.c |
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pmn_deriv.c |
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pmn_driver.c |
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pmn_reader.c |
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pmn_runge_kutta.c
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pmn_subs.h
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Last modified August 16th, 2003 by Behrang Amini. Please feel
free to contact me at mailto:zyryab@rice.edu?subject=PMN
Model Web Page with any questions regarding these files.
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