Abstract
Interstitial cells of Cajal (ICC) act as pacemaker cells in the gastrointestinal tract by generating electrical slow waves to regulate rhythmic smooth muscle contractions. Intrinsic Ca2+ oscillations in ICC appear to produce the slow waves by activating pacemaker currents, currently thought to be carried by the Ca2+-activated Cl- channel anoctamin 1 (Ano1). In this article we present a novel model of small intestinal ICC pacemaker activity that incorporates store-operated Ca2+ entry and a new model of Ano1 current. A series of simulations were carried out with the ICC model to investigate current controversies about the reversal potential of the Ano1 Cl- current in ICC and to predict the characteristics of the other ion channels that are necessary to generate slow waves. The model results show that Ano1 is a plausible pacemaker channel when coupled to a store-operated Ca2+ channel but suggest that small cyclical depolarizations may still occur in ICC in Ano1 knockout mice. The results predict that voltage-dependent Ca2+ current is likely to be negligible during the slow wave plateau phase. The model shows that the Cl- equilibrium potential is an important modulator of slow wave morphology, highlighting the need for a better understanding of Cl- dynamics in ICC.
Original language | English (US) |
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Pages (from-to) | G711-G727 |
Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 306 |
Issue number | 8 |
DOIs | |
State | Published - Apr 15 2014 |
Keywords
- Anoctamin 1
- Interstitial cells of Cajal
- Mathematical model
- Storeoperated calcium entry
ASJC Scopus subject areas
- Physiology
- Hepatology
- Gastroenterology
- Physiology (medical)