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In the past two decades, we have identified several functional abnormalities of mutant ion channels and their associated transmissions using several experiments involving single\u2010cell and genetic animal (rodent) models. Currently, epileptologists understand that functional abnormalities underlying epileptogenesis\/ictogenesis in humans and rodents are more complicated than previously believed and that the function of mutant molecules alone cannot contribute to the development of epileptogenesis\/ictogenesis but play important roles in the development of epileptogenesis\/ictogenesis through formation of abnormalities in various other transmission systems before epilepsy onset. Based on our recent findings using genetic rat ADSHE models, harbouring <jats:italic>Chrna4<\/jats:italic> mutant, corresponding to human S284L\u2010mutant <jats:italic>CRHNA4<\/jats:italic>, this review proposes a hypothesis associated with tripartite synaptic transmission in ADSHE pathomechanisms induced by mutant ACh receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Building Bridges in Neuropharmacology. 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