A QUANTITATIVE MODEL OF THE SIP SYNCYTIUM

Abstract

In the SIP syncytium, interstitial cells, such as interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells, are electrically coupled to smooth muscle cells. A balance between excitatory and inhibitory influences from the interstitial cells is believed to maintain the basal excitability of the gastrointestinal (GI) musculature. In this work, we aim to describe electrical activity in the SIP syncytium. First, we constructed a phenomenological model describing Ca2+ transients in PDGFRα+ cells and investigated their effect on tonic inhibition in the GI musculature. Second, we constructed a biophysically-based intramuscular ICC (ICC-IM) model describing their role in mediating cholinergic neurotransmission and adapted our Ca2+ transient model for the ICC-IM model to study its depolarizing influence on the GI musculature. Finally, we developed a framework to model tissue electrophysiology with three cell types to integrate the excitatory and inhibitory effects from the interstitial cells on the GI musculature.