A mathematical model of pacemaker activity recorded from mouse small intestine
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This CellML version of the model runs in both COR and PCEnv. Although the model produces pacemaker potentials, there are discrepancies between the original and the CellML model - including a different behaviour at the resting membrane potential and a different frequency of generation of slow waves. The units have been checked and are consistent. We'd like to acknowledge Nandita Carvalho for providing us with access to her Matlab code, which played a critical role in the process of successfully translating the model into CellML. Also Alberto Corrias for his feedback on the CellML model
Model Structure
Phasic gastrointestinal (GI) muscle is able to autonomously generate rhythmic contractions independent of the enteric nervous system. The electrical activity that generates these rhythmic contractions are called slow waves, or pacemaker potentials (PP), and they are produced by a specialised group of pacemaker cells called Insterstitial Cells of Cajal (ICC). Pacemaker potentials pass via gap junctions from the ICC to smooth muscle cells (SMC), activating L-type Ca2+ channels, Ca2+ influx and the contraction of the SMC.
In the study described here, Jae Boum Youm et al. have developed a mathematical model which quantitatively describes the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC pacemaker unit. The model includes seven major currents that flow across the ICC membrane to transport three ions, Na+, Ca2+ and K+ (see the figure below). These currents include: the inward rectifier current (Ik1), L-type Ca2+ current (ICaL), voltage-dependent and dihydropyridine-resistant current (IVDDR), autonomous inward current. (IAI), Na+/Ca2+ exchanger current, (INaCa), Na+/K+ pump current (INaK), and the plasmalemmal Ca2+ pump current (IPMCA).
It should be noted that the model described here in CellML is not identical to the published model. Instead, it represents the working model written in Matlab by Nandita Carvalho, who carried out an extensive literature review and had personal correspondence with the author of the original model Jae Boum Youm. On comparison, the final model was able to replicate experimental results and hence it was used to make predictions of slow wave characteristics of the small intestine.
model diagram
A schematic diagram of the cell model. There are 7 membrane currents. IVDDR is known to be responsible for propagation and its influx into the cell causes a slight depolarisation which increases the probability of Ca2+release from th SR through IP3-gated channels. This further depolarises the cell causing an influx of ions into the cell (via the pacemaker current IAI), which the initiates the slow wave.
The complete original paper reference is cited below:
A mathematical model of pacemaker activity recorded from mouse small intestine, Jae Boum Youm, Nari Kim, Jin Han, Euiyong Kim, Hyun Joo, Chae Hun Leem, Gazunori Goto, Akinori Noma, and Yung E. Earm, 2006,
Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences
, 364, 1135-1154. (Full text and PDF versions of the article are available to journal subscribers on the Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences website.) PubMed ID: 16608700
I_CaL
L-type calcium current
I_CaL_m_gate
L-type calcium current m gate
I_CaL_h_gate
L-type calcium current h gate
I_VDDR
voltage-dependent and DHP-resistant current
I_VDDR_m_gate
voltage-dependent and DHP-resistant current m gate
I_VDDR_h_gate
voltage-dependent and DHP-resistant current h gate
I_AI
autonomous inward current
I_NaCa
sodium calcium exchange current
I_NaCa_y_gate
sodium calcium exchange current y gate
I_NaK
sodium potassium pump current
I_PMCA
plasmalemmal calcium pump current
I_up
SR calcium pump current
I_up_y_gate
SR calcium pump current y gate
I_tr
calcium transfer from the SR uptake site to the release site
I_leak
calcium leak from the SR
I_IP3R
IP3-mediated calcium release from the SR
calcium_concentrations_in_the_SR
calcium concentrations in the SR
IP3_metabolism
IP3 metabolism
electrophysiology
gastric
small intestine
pacemaker
interstitial cells of Cajal
ICC
Hyun
Joo
The University of Auckland, Bioengineering Institute
A mathematical model of pacemaker activity recorded from mouse small intestine
364
1135
1154
Nari
Kim
This is a CellML description of Youm et al.'s 2006 mathematical model of pacemaker activity recorded from mouse small intestine.
Philosophical transactions of the Royal Society of London. Series A, Mathematical and physical sciences
Gazunori
Goto
Jin
Han
Youm et al.'s 2006 mathematical model of pacemaker activity recorded from mouse small intestine.
keyword
Euiyong
Kim
2006-05-15
c.lloyd@auckland.ac.nz
16608700
Catherine
Lloyd
May
Akinori
Noma
Jae
Youm
Boum
Yung
Earm
E
Catherine Lloyd
This CellML version of the model runs in both COR and PCEnv to replicate the published results. The units have been checked and are consistent. We'd like to acknowledge Nandita Carvalho for providing us with access to her Matlab code, which played a critical role in the process of successfully translating the model into CellML.
The University of Auckland
The Bioengineering Institute
Chae
Leem
Hun
Catherine Lloyd
2007-11-06T00:00:00+00:00