A mechanistic model of a PDGFRα+ cell

Abstract

A novel platelet-derived growth factor receptor alpha-positive cell (PDGFRα+) has recently been identified as part of the purinergic inhibitory neural control mechanism in the gastrointestinal (GI) tract. The mechanism through which PDGFRα+ cells mediate GI muscle relaxation has been found to be associated with the purine receptors P2Y1 and apamin-sensitive SK3 channels that are highly expressed in these cells. This study aims to develop a mechanistic model elucidating a proposed mechanism through which PDGFRα+ cells contribute to purinergic inhibitory neuromuscular transmission. In accordance with recent experimental findings, the model describes how the binding of neurotransmitters, released from enteric neurons, triggers the release of Ca2+ from the endoplasmic reticulum in the PDGFRα+ cells, and how this subsequently leads to large amplitude transient outward currents, which in turn hyperpolarize the cell. The model has been validated against experimental recordings and good agreement was found under normal and pharmacologically-altered conditions. This model demonstrates the feasibility of the proposed mechanism and provides a basis for understanding the mechanism underlying purinergic control of colonic motility.