A biophysical model of intestinal motility: Application in pharmacological studies

Abstract

A biophysical model of the myoelectrical activity of the small intestine is presented. Based on real morphological and electrophysiological data, the model assumes that: the intestine is an electromyogenic syncytium; the kinetics of L- and T-type Ca²⁺, Ca²⁺-activated K⁺, voltage dependent K⁺ and Cl⁻ channels determines the electrical activity; the enteric nervous system is represented by afferent and efferent cholinergic pathways that provide an excitatory input through receptor linked L-type Ca²⁺ channels; the dynamics of propagation of the wave of depolarization along the axons satisfies the Hodgkin-Huxley model; the electrical activity of the neural soma reflects the interaction of N-type Ca²⁺ channels, Ca²⁺-activated K⁺ and voltage dependent Na⁺, K⁺ and Cl⁻ channels; the smooth muscle syncytium is a nulldimensional contractile system. With the proposed model the dynamics of active force generation is determined entirely by the concentration of cytosolic calcium. We used the model to analyze mechanisms underlying benzodiazepine-induced adynamic ileus at cellular and subcellular levels. The model displays quantitative changes in component processes, otherwise inperceptible, which explain the origin of this clinical problem.