A Model of Sinoatrial Node Vagal Control
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This model is valid CellML. It has been unit checked and curated and is known to reproduce the published results in COR and OpenCell.
Model Structure
Sinoatrial (SA) node cells have an inherent ability to generate a depolarising, unstable resting potential leading to automaticity. The rhythmic, electrical activity of the sinoatrial cells set the rate at which the entire heart beats, hence the sinoatrial node myocytes are referred to as the pacemaker cells. This cardiac pacemaker activity is under vagal control. The ionic mechanisms underlying the vagal inhibition of the cardiac pacemaker are the subject of investigation in a mathematical model published by Socrates Dokos, Branko Celler and Nigel Lovell (1996).
In this paper, the authors review the existing knowledge surrounding the vagal control of sinoatrial rhythm. It is known that following vagal stimulation, acetylcholine (ACh) is released into the parasympathetic neuroeffector junction, and then binds to muscarinic receptors on the plasma membrane of the SA node cells. This receptor-binding triggers membrane hyperpolarisation, and/or decreases the rate of pacemaker depolarisation, in turn prolonging the spontaneous cycle duration, and decreasing the rate of autorhythmic firing. The principal mechanism underlying this ACh-mediated inhibition of the cardiac pacemaker is an increase in the membrane permeability to K+. However, it has been suggested that the influence of ACh on other ion currents may also have a significant effect on pacemaker activity.
The focus of the Dokos et al. 1996 model was to gain a better understanding of the mechanisms underlying vagal control of the cardiac pacemaker. Their model was based on a wide range of electrophysiological data, and their aim was to reproduce these experimental results with their mathematical model. This model is an extension of their previously published mathematical model of the SA node. In this new model, the background potassium current ib,K
has been replaced by an ACh-activated potassium current iK,ACh
. In addition, the new model incorporates the influence of ACh on the other ionic currents, such as the inhibition of the hyperpolarisation-activated current if
, and the inhibition of the L-type calcium current iCa,L
.
Vagal control of pacemaker activity is modelled using a three compartment model describing ACh release and uptake in the neuroeffector junction (see below). Upon vagal stimulus, ACh is released into the neuroeffector junction, activating iK,ACh
and inhibiting if
and iCa,L
.
The complete original paper reference is cited below:
Vagal Control of Sinoatrial Rhythm: a Mathematical Model, Socrates Dokos, Branko Celler, and Nigel Lovell, 1996,
Journal of Theoretical Biology
, 182, 21-44. PubMed ID: 8917735
cell diagram
A schematic diagram of the Dokos et al. 1996 mathematical model of vagal control of cardiac pacemaker activity.
Sinoatrial Node
cardiac
electrophysiology
The University of Auckland, Bioengineering Institute
2003-04-15T00:00:00+00:00
Catherine
Lloyd
May
Branko
Celler
2003-06-04
8917735
Catherine Lloyd
Socrates
Dokos
Nigel
Lovell
keyword
c.lloyd@auckland.ac.nz
Added equations for k14, k41, di, k34, k21, k23, k32, and do in the sodium-calcium exchange current component.
Peter
Villiger
J
Dokos et al's 1996 mathematical model of the ion currents underlying the
vagal inhibition of cardiac sinoatrial node pacemaker activity.
Sinoatrial Node Cell
Mammalia
This is the CellML description of Dokos et al's 1996 mathematical model of the ion currents underlying the vagal inhibition of cardiac sinoatrial node pacemaker activity.
The University of Auckland
The Bioengineering Institute
2005-04-20
1996-09-07
2002-07-18
Catherine
Lloyd
May
Vagal Control of Sinoatrial Rhythm: a Mathematical Model
182
21
44
Made MathML id's unique
Journal of Theoretical Biology
Corrected equations: i_CaL_calculation in L_type_calcium_current and
i_CaT_calculation in T_type_calcium_current.
Catherine
Lloyd
May