Modelling The Effect Of Intracellular Ca2+ On Sinoatrial Node Action Potentials, 2001
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This model is valid CellML. However the model will not run in either OpenCell or COR and the model requires further curation.
Model Structure
ABSTRACT: The possible effects of intracellular Ca2+ on the pacemaker of the heart, the sinoatrial node, are reviewed. In mammalian sinoatrial node, reduction or abolition of the intracellular Ca2+ transient by ryanodine, sarcoplasmic reticulum Ca2+ pump block or 1,2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid (BAPTA) reduces the spontaneous rate by 21-32%, whereas in amphibian sinus venosus it abolishes spontaneous activity. In rabbit sinoatrial node, ryanodine/BAPTA reduces the T-type Ca2+ current (iCa,T), perhaps slows inactivation of the L-type Ca2+ current (iCa,L), reduces the inward Na+-Ca2+ exchange current (iNaCa), and reduces the rapid and slow delayed rectifier K+ currents (iK,r and iK,s, respectively). Other evidence shows that a reduction of intracellular Ca2+ inhibits the hyperpolarization-activated current (if). These putative intracellular Ca2+-dependent changes in ionic currents have been incorporated into different models of rabbit sinoatrial node action potentials. In the models, block of the Ca2+ transient reduced the spontaneous rate by 24 and 26% in the central and peripheral models of Zhang and others, 13% in the Oxsoft model (Noble et al.), 9% in the model of Wilders and others, and 41% in the model of Demir and others. In all models, the reduction in rate was not primarily the result of the decrease in iNaCa, but instead the combination of all changes in ionic currents.
The original paper reference is cited below:
Control of the pacemaker activity of the sinoatrial node by intracellular Ca2+. Experiments and modelling, M.R. Boyett, H. Zhang, A. Garny and A.V. Holden, 2001, Phil. Trans. R. Soc. Lond. A., 359, 1091-1110. (note there is no PubMed ID for this publication).
cell diagram of the Boyett et al SAN model showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum
A schematic diagram describing the current flows across the cell membrane that are captured in the Boyett et al 2001 model of the action potentials in the peripheral cells of the SA node.
This is the CellML description of Boyett et al's mathematical model of pacemaker activity in the sinoatrial node. Their model is a development of Zhang et al's earlier 2000 model of action potentials in SA node cells by considering intracellular Ca2+ handling. The SA node is functionally, anatomically and electrophysiologically heterogeneous. Boyett et al have considered this heterogeneity and they define two distinct models for the peripheral SA node and the central SA node. These models have the same equations but they vary in their parameters. Below is a CellML description of the model of action potentials in the periphery of the sinoatrial(SA) node. For a model of the central SA node action potential, use the equations below but substitute some parameters with the appropriate ones listed in the original paper.
Catherine
Lloyd
May
The University of Auckland, Auckland Bioengineering Institute
2002-07-19
The sodium current was originally thought to be absent in SA node
cells and consequently, most of the earlier models of the SA node
action potential do not include i_Na. However, more recent
experimental results show that i_Na is present and that it is
physiologically important. The sodium channel has one activation
gate m and one inactivation gate which has two components, a fast and
a slow inactivation variable; h1 and h2.
James
Lawson
Richard
Experimental evidence suggests that intracellular calcium controls a
number of ionic currents. Boyett et al incorporated intracellular
calcium handling into the model of Zhang et al (2000).
Boyett et al's 2001 mathematical model of control of pacemaker
activity of the sinoatrial node
Sinoatrial Node Cell
keyword
pacemaker
atrial myocyte
calcium dynamics
electrophysiology
cardiac
sinoatrial node
A.
Garny
In their model, Boyett et al added the sustained inward current
described by Guo et al (1995) and Shinagawa et al (2000) in rabbit
and rat SA node cells. The equations defined below are taken from
Shinagawa et al (2000).
H.
Zhang
Philosophical Transactions of The Royal Society, Mathematical, Physical and Engineering Sciences
2002-01-28T00:00:00+00:00
A
V
Holden
M
R
Boyett
Added more metadata.
Other SA node models have included computation of concentrations of
intracellular Na+ and Ca2+. In this model, Zhang et al have assumed
that all ion concentrations remain constant.
2009-05-28T15:58:34+12:00
Control of the pacemaker activity of the sinoatrial node by intracellular Ca2+. Experiments and modelling
359
1045
1337
The University of Auckland
Auckland Bioengineering Institute
The slow sigmoidal activation of i_K_s is modelled by squaring the
gating variable xs. The i_K_s channel is also slightly permeable to
Na+ ions.
2002-02-25
i_f is a mixed current composed of both Na+ and K+ ions. In the
equation to describe i_f, Zhang et al included i_f_Na and i_f_K as
separate components and they also included a single activation
variable y.
fixed e-notation errors
updated curation status
removed reference link in documentation
The potassium cuurent in rabbit SA node cells can be divided into two
kinetically different components, a fast cuurent i_K_r and a slow
current i_K_s. Activation and inactivation of i_K_r has
double-exponential time courses. To model this, Zhang et al have
used two activation variables; a fast one (P_a_f) and a slow one
(P_a_s). There is a single inactivation variable P_i.
i_to and i_sus are respectively the transient and sustained
components of the 4-Aminopyridine-sensitive current. The current has
an activation variable r and and inactivation variable q.
Catherine Lloyd
Corrected several equations.
The L-type calcium channel has two gates, an activation gate d_L and
an inactivation gate f_L.
Catherine
Lloyd
May
2001-01-01
Peter
Villiger
J
Updated syntax to conform with cellml1.1 specs
2005-04-20
The T-type calcium channel has two gates, an activation gate d_T and
an inactivation gate f_T.
c.lloyd@auckland.ac.nz
Catherine
Lloyd
May