MODELLING ENTERIC INHIBITORY NEUROMUSCULAR TRANSMISSION IN THE HUMAN COLON

Abstract

WE HAVE DEVELOPED COMPUTATIONAL MODELS TO STUDY THE INFLUENCE OF ENTERIC INHIBITORY NEUROMUSCULAR TRANSMISSION ON THE ELECTROPHYSIOLOGY OF HUMAN COLONIC SMOOTH MUSCLE CELLS. FIRST, WE HAVE CONSTRUCTED A BIOPHYSICALLY-BASED HUMAN COLONIC SMOOTH MUSCLE CELL (HCSMC) MODEL, WHICH CAN REPRODUCE ELECTRICAL SLOW-WAVE ACTIVITY. SECOND, WE HAVE DEVELOPED A MECHANISTIC MODEL TO DESCRIBE THE ROLE OF A NOVEL PLATELET-DERIVED GROWTH FACTOR RECEPTOR ALPHA-POSITIVE CELL (PDGFRA+ CELL) IN THE PURINERGIC INHIBITORY NEURAL CONTROL OF COLONIC MOTILITY. THIRD, WE HAVE EXTENDED THE HCSMC MODEL TO INCORPORATE A DESCRIPTION OF NITRERGIC INTRACELLULAR REGULATORY PATHWAY. FINALLY, WE INTEGRATED BOTH INHIBITORY NEUROMUSCULAR TRANSMISSIONS TO RECONSTRUCT THE EXPERIMENTALLY OBSERVED BIPHASIC INHIBITORY JUNCTION POTENTIAL (IJP) AND EXAMINED THEIR INDIVIDUAL INHIBITORY RESPONSES ON HUMAN COLONIC MOTILITY BY INCORPORATING AN ACTIVE MECHANICS MODEL. OUR MODELS PROVIDE A BASIS FOR A MORE DETAILED UNDERSTANDING OF THE