BIOPHYSICAL THEORY AND MODELING |
A Biophysically Based Mathematical Model of Unitary Potential Activity in Interstitial Cells of Cajal
Richard A Faville 1*, Andrew J Pullan 1, Kenton M Sanders 2 and Nicolas P Smith 1
1 The Auckland Bioengineering Institute, University of Auckland, Auckland, NZ
2 Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557,
* To whom correspondence should be addressed. E-mail: r.faville{at}auckland.ac.nz.
Submitted on September 20, 2007
Revised on November 5, 2007
Accepted on 15 February 2008
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Abstract |
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Unitary potential (UP) depolarisations are the basic intracellular events responsible for pacemaker activity in Interstitial Cells of Cajal (ICC), and are generated at intracellular sites termed "pacemaker units". In this study, we present a mathematical model of the trans-membrane ion flows and intracellular Ca2+ dynamics from a single ICC pacemaker unit acting at near resting membrane potential. This model quantitatively formalises the framework of a novel ICC pacemaking mechanism that has recently been proposed. Model simulations produce spontaneously rhythmic UP depolarisations with amplitude of approximately 3 mV at a frequency of 0.05 Hz. The model predicts that the main inward currents, carried by a Ca2+-inhibited non-selective cation conductance, are activated by depletion of sub-plasma membrane [Ca2+] caused by Sarco-Endoplasmic Reticulum Calcium ATPase Ca2+ sequestration. Furthermore, pacemaker activity predicted by our model persists under simulated voltage clamp and is independent of [IP3] oscillations. The model presented here provides a basis to quantitatively analyse UP depolarisations and the biophysical mechanisms underlying their production.
Key Words:
Intracellular Ca2+ Dynamics, Mathematical Modelling, Slow Waves
