Emergence of Pathological Slow Waves due to Elevated Neurotransmitter Release

A physiologically based computational framework was used to develop a novel gastric motility network model. Along with the widely assumed electrical gap junction coupling between the pacemaker and muscle cells as well as the second messenger molecules, in this model we also included a rostro-caudal linear decreasing gradient of neural stimulus to the pacemakers along the length of the stomach to mimic enteric neurotransmitter release and an increasing gradient of muscarinic receptor density. We find that aberrant responses of different parts of the stomach (corpus, antrum etc.) to exogenous application of excitatory neurotransmitters such as Acetylcholine, can be explained by an interplay between the level of neurotransmitter and density of receptors available. This model can also explain anomalous behavior such as retrograde propagation and functional uncoupling in the entire stomach in response to external neuro-agonists.