A Model of Slow Wave Propagation and Entrainment Along the Stomach

Abstract

Interstitial cells of Cajal (ICC) isolated from different regions of the stomach generate spontaneous electrical slow wave activity at different frequencies, with cells from the proximal stomach pacing faster than their distal counterparts. However, in vivo there exists a uniform pacing frequency; slow waves propagate aborally from the proximal stomach and subsequently entrain distal tissues. Significant resting membrane potential (RMP) gradients also exist within the stomach whereby membrane polarization generally increases from the fundus to the antrum. Both of these factors play a major role in the macroscopic electrical behavior of the stomach and as such, any tissue or organ level model of gastric electrophysiology should ensure that these phenomena are properly described. This study details a dual-cable model of gastric electrical activity that incorporates biophysically detailed single-cell models of the two predominant cell types, the ICC and smooth muscle cells. Mechanisms for the entrainment of the intrinsic pacing frequency gradient and for the establishment of the RMP gradient are presented. The resulting construct is able to reproduce experimentally recorded slow wave activity and provides a platform on which our understanding of gastric electrical activity can advance.

A theoretical study of the initiation, maintenance and termination of gastric slow wave re-entry

“…A number of recent multi-scale modeling studies have adopted continuum approaches to model a voltage-dependent mediation of slow wave entrainment in an ICC network (Buist, Corrias et al 2010; Du, O'Grady et al 2010). In this study, a similar approach using the monodomain model was used as the governing equation (Eq.…”

“…The cell model employed in this study represents a voltage-dependent inositol 1,4,5-trisphosphate (IP 3 ) mechanism of entrainment (Imtiaz, Smith et al 2002; Koh, Ward et al 2003). Other alternative entrainment mechanisms include unitary potentials and Ca 2+ -sensitive Cl − conductance, which were considered in other cell modeling studies (Faville, Pullan et al 2009; Buist, Corrias et al 2010), but they were not employed in this study due to computational efficiency (Lees-Green, Du et al 2011). …”

“…Another important aspect of the voltage-dependent IP 3 entrainment mechanism is the response of the cell model to an extrinsic stimulus, either in the form of a current stimulus or slow wave potentials from neighboring tissues (Buist, Corrias et al 2010; Du, O'Grady et al 2010). To this end, the responses of the cell model at an intrinsic frequency of 3 cpm to a series of stimuli (single pulse; amplitude: 30 pA; duration: 350 ms) at six different onset times were also characterized (Fig.…”

“…Previous modeling studies have investigated entrainment of slow waves in a one-dimensional model (Buist, Corrias et al 2010; Du, O'Grady et al 2010). However, because a modified cell model was used in this study and the baseline simulations were fitted to two species with different intrinsic frequencies, additional changes to the model were required to demonstrate entrainment.…”

Experimental evidence and mathematical modeling of thermal effects on human colonic smooth muscle contractility

“…Other cumulative and coupled factors could also be studied, such as stretch-induced contractions of external electrical stimulations (19,54). From a modeling point of view, a forthcoming work in this direction will deal with realistic intestinal geometries with space-dependent dynamics of slow wave propagation and entrainment on the line of previous theoretical and experimental works (14,39,45,72). More complex Ca 2ϩ dynamics will be considered in the nonlinear coupling, with both mechanical quantities and temperature gradients.…”