A Model Of Parasympathetic Modulation Of Pacemaker Rate, 1999
Penny
Noble
Oxford University
Model Status
This model has been validated by Penny Noble of Oxford University and is known to run in COR and OpenCell to reproduce the published results. The units have been checked and are balanced.
Model Structure
ABSTRACT: We have extended our compartmental model [Am. J. Physiol. 266 (Cell Physiol. 35): C832-C852, 1994] of the single rabbit sinoatrial node (SAN) cell so that it can simulate cellular responses to bath applications of ACh and isoprenaline as well as the effects of neuronally released ACh. The model employs three different types of muscarinic receptors to explain the variety of responses observed in mammalian cardiac pacemaking cells subjected to vagal stimulation. The response of greatest interest is the ACh-sensitive change in cycle length that is not accompanied by a change in action potential duration or repolarization or hyperpolarization of the maximum diastolic potential. In this case, an ACh-sensitive K+ current is not involved. Membrane hyperpolarization occurs in response to much higher levels of vagal stimulation, and this response is also mimicked by the model. Here, an ACh-sensitive K+ current is involved. The well-known phase-resetting response of the SAN cell to single and periodically applied vagal bursts of impulses is also simulated in the presence and absence of the beta-agonist isoprenaline. Finally, the responses of the SAN cell to longer continuous trains of periodic vagal stimulation are simulated, and this can result in the complete cessation of pacemaking. Therefore, this model is 1) applicable over the full range of intensity and pattern of vagal input and 2) can offer biophysically based explanations for many of the phenomena associated with the autonomic control of cardiac pacemaking.
The original paper reference is cited below:
Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model, Semahat S. Demir, John W. Clark and Wayne R. Giles, 1999,
American Journal of Physiology, 276, H2221-H2244. PubMed ID: 10362707
cell diagram of the Demir et al SAN model showing ionic currents, pumps and exchangers within the sarcolemma
A schematic diagram describing the current flows across the cell membrane that are captured in the Demir et al 1999 model of the electrophysiological activity in a SAN cell.
cardiac
signal transduction
sinoatrial node
electrophysiology
The University of Auckland, Bioengineering Institute
Autumn
Cuellar
A
added cmeta:id's for some variables to allow referencing by PCEnv session
Peter
Villiger
J
2002-07-18
The University of Auckland
The Bioengineering Institute
This model has been validated by Penny Noble of Oxford University.
Catherine Lloyd
Corrected several equations.
The effects of ACh and Iso on i_Ca_L and i_K are produced indirectly via the cAMP-dependent modulation of L-type Ca2+ and K+ channel
conductance (g_Ca_L and g_K) respectively.
Catherine
Lloyd
May
2002-07-18
Corrected some units.
Catherine
Lloyd
May
Added more metadata.
2002-02-28
2007-12-19T13:48:43+13:00
Below is a CellML description of Demir et al's 1999 mathematical model of parasympathetic modulation of sinoatrial node (SAN) pacemaker activity in a rabbit heart. Based on experimental data, this model is a development of their earlier model of the single rabbit SAN cell (1994). Modifications have been made enabling it to mimic the important effects of the second-messenger cAMP and to simulate the response of SAN cells to the neurotransmitter acetylcholine (ACh) and isoprenaline (Iso).
keyword
John
Clark
W
Semahat
Demir
S
c.lloyd@auckland.ac.nz
2005-04-25
i_f is modulated via a direct effect of cAMP on the
voltage-dependence of its steady-state activation variable y.
2
100000
0.1
Catherine
Lloyd
May
Changed equivalent to eq in apply id line.
ACh has a direct stimulatory affect on the ACh-sensitive potassium
channel. The G-protein-mediated, direct affect of ACh on i_K_ACh
occurs via the extrajunctional M2/K_ACh muscarinic receptor. This
channel has a single gating variable a.
2003-04-05
James Lawson
This model has been validated by Penny Noble of Oxford University and is known to run in COR and PCEnv. A PCEnv session file is also associated with this version. Model curated by Penny Noble using Demir 1994 Oxsoft Heart model code and Demir 1999 paper.
1999-06-01
Catherine
Lloyd
May
The T-type calcium channel has two gates, an activation gate d_T and an inactivation gate f_T.
The effects of Iso on i_NaK may be species dependent as it has been observed that Iso directly stimulates Na+-K+-ATPase activity in rabbit ventricular myocytes (Desilets and Baumgarten, 1986), but indirectly stimulates i_NaK in guinea pig ventricular myocytes via a PKA phosphorylation step (Gao et al. 1992, 1994). In the absence of any quantitative evidence, in this model Demir et al. have assumed that cAMP directly stimulates i_NaK in the rabbit SAN cell and that this cAMP dependency may be modelled by the equations below.
American Journal of Physiology
Wayne
Giles
R
Changed sign of i_rel in dCai-dt equation. Changed the name of sodium-calcium pump to an exchanger. Changed U_calculation from an equals sign to an equivalent sign.
Changed the model name so the model loads in the database easier.
Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model
276
H2221
H2244
2002-02-25
Sinoatrial Node Cell
Demir et al's 1999 mathematical model of a rabbit sinoatrial node cell
Rabbit
2002-02-06T00:00:00+00:00
10362707
James
Lawson
Richard
2007-06-19T15:32:11+12:00
Catherine
Lloyd
May
Penny
Noble
J