Referenced in: none

Automatically associated channels: Slo1

Title: Computational modeling of anoctamin 1 calcium-activated chloride channels as pacemaker channels in interstitial cells of Cajal.

Authors: Rachel Lees-Green, Simon J Gibbons, Gianrico Farrugia, James Sneyd, Leo K Cheng

Journal, date & volume: Am. J. Physiol. Gastrointest. Liver Physiol., 2014 Apr 15 , 306, G711-27

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24481603

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 Ca(2+) oscillations in ICC appear to produce the slow waves by activating pacemaker currents, currently thought to be carried by the Ca(2+)-activated Cl(-) channel anoctamin 1 (Ano1). In this article we present a novel model of small intestinal ICC pacemaker activity that incorporates store-operated Ca(2+) 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 Ca(2+) channel but suggest that small cyclical depolarizations may still occur in ICC in Ano1 knockout mice. The results predict that voltage-dependent Ca(2+) 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.