Acetylcholine,the main enteric excitatory neuromuscular transmitter,evokes mem-brane depolarization and contraction of gastrointestinal smooth muscle cells byactivating G protein-coupled muscarinic receptors.Although the cholinergic exci-tation is generally underlined by the multiplicity of ion channel effects,the pri-mary event appears to be the opening of cation-selective channels;among themthe 60 pS channel has been recently identified as the main target for the acetylcho-line action in gastrointestinal myocytes.The evoked cation current,termed mI_(CAT),causes either an oscillatory or a more sustained membrane depolarization response,which in turn leads to increases of the open probability of voltage-gated Ca~(2+)channels,thus providing Ca~(2+)entry in parallel with Ca~(2+)release for intracellularCa~(2+)concentration rise and contraction.In recent years there have been severalsignificant developments in our understanding of the signaling processes under-lying mI_(CAT)generation.They have revealed important synergistic interactionsbetween M_2 and M_3 receptor subtypes,single channel mechanisms,and the in-volvement of TRPC-encoded proteins as essential components of native musca-rinic cation channels.This review summarizes these recent findings and in par-ticular discusses the roles of the phospholipase C/InsP_3/intracellular Ca~(2+)releasesystem in the mI_(CAT)physiological regulation. Acetylcholine, the main enteric excitatory neuromuscular transmitter, evokes mem-brane depolarization and contraction of gastrointestinal smooth muscle cells by activating G protein-coupled muscarinic receptors. Although the cholinergic exci-tation is generally underlined by the multiplicity of ion channel effects, the pri-mary event appears to be the opening of cation-selective channels; among them the 60 pS channel has been recently identified as the main target for the acetylcho-line action in gastrointestinal myocytes. evoked cation current, termed mI_ (CAT), causes either an oscillatory or a more sustained membrane depolarization response, which in turn leads to increases of the open probability of voltage-gated Ca 2+ channels, thus providing Ca 2+ entry in parallel with Ca 2+ release for In recent years there have been severalsignificant developments in our understanding of the signaling processes under-lying mI_ (CAT) generation.The intracellular Ca ~ (2+) concentration rise and contraction. y have revealed important synergistic interactions between M_2 and M_3 receptor subtypes, single channel mechanisms, and the in-volvement of TRPC-encoded proteins as essential components of native musca-rinic cation channels. This review summarizes these recent findings and in par- ticular discuss the roles of the phospholipase C / InsP_3 / intracellular Ca 2+ release system in the mI_ (CAT) physiological regulation.