ABSTRACT:
This a model from the article:
Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks
confers robust and flexible pacemaker function in a novel pacemaker cell model.
Maltsev VA, Lakatta EG. Am J Physiol Heart Circ Physiol
2009 Mar;296(3):H594-615 19136600
,
Abstract:
Recent experimental studies have demonstrated that sinoatrial node cells (SANC)
generate spontaneous, rhythmic, local subsarcolemmal Ca(2+) releases (Ca(2+)
clock), which occur during late diastolic depolarization (DD) and interact with
the classic sarcolemmal voltage oscillator (membrane clock) by activating
Na(+)-Ca(2+) exchanger current (I(NCX)). This and other interactions between
clocks, however, are not captured by existing essentially membrane-delimited
cardiac pacemaker cell numerical models. Using wide-scale parametric analysis of
classic formulations of membrane clock and Ca(2+) cycling, we have constructed
and initially explored a prototype rabbit SANC model featuring both clocks. Our
coupled oscillator system exhibits greater robustness and flexibility than
membrane clock operating alone. Rhythmic spontaneous Ca(2+) releases of
sarcoplasmic reticulum (SR)-based Ca(2+) clock ignite rhythmic action potentials
via late DD I(NCX) over much broader ranges of membrane clock parameters [e.g.,
L-type Ca(2+) current (I(CaL)) and/or hyperpolarization-activated ("funny")
current (I(f)) conductances]. The system Ca(2+) clock includes SR and
sarcolemmal Ca(2+) fluxes, which optimize cell Ca(2+) balance to increase
amplitudes of both SR Ca(2+) release and late DD I(NCX) as SR Ca(2+) pumping
rate increases, resulting in a broad pacemaker rate modulation (1.8-4.6 Hz). In
contrast, the rate modulation range via membrane clock parameters is
substantially smaller when Ca(2+) clock is unchanged or lacking. When Ca(2+)
clock is disabled, the system parametric space for fail-safe SANC operation
considerably shrinks: without rhythmic late DD I(NCX) ignition signals membrane
clock substantially slows, becomes dysrhythmic, or halts. In conclusion, the
Ca(2+) clock is a new critical dimension in SANC function. A synergism of the
coupled function of Ca(2+) and membrane clocks confers fail-safe SANC operation
at greatly varying rates.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Maltsev VA, Lakatta EG. (2009) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
Camille Laibe 
