Open AccessRegulation of TRP‐like muscarinic cation current in gastrointestinal smooth muscle with special reference to PLC/InsP 3 /Ca 2+ system
Author(s) -
ZHOLOS Alexander V
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00392.x
Subject(s) - trpc , muscarinic acetylcholine receptor , depolarization , acetylcholine , stretch activated ion channel , chemistry , microbiology and biotechnology , biophysics , myocyte , excitatory postsynaptic potential , intracellular , neuroscience , ion channel , biology , transient receptor potential channel , endocrinology , voltage gated ion channel , receptor , biochemistry
Acetylcholine, the main enteric excitatory neuromuscular transmitter, evokes membrane depolarization and contraction of gastrointestinal smooth muscle cells by activating G protein‐coupled muscarinic receptors. Although the cholinergic excitation is generally underlined by the multiplicity of ion channel effects, the primary 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 acetylcholine action in gastrointestinal myocytes. The evoked cation current, termed m I 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 intracellular Ca 2+ concentration rise and contraction. In recent years there have been several significant developments in our understanding of the signaling processes underlying m I CAT generation. They have revealed important synergistic interactions between M 2 and M 3 receptor subtypes, single channel mechanisms, and the involvement of TRPC‐encoded proteins as essential components of native muscarinic cation channels. This review summarizes these recent findings and in particular discusses the roles of the phospholipase C/InsP 3 /intracellular Ca 2+ release system in the m I CAT physiological regulation.