Regulation of TRP-like muscarinic cation current in gastrointestinal smooth muscle with special reference to PLC/InsP3/Ca2+ system.
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 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 Ca2+ channels, thus providing Ca2+ entry in parallel with Ca2+ release for intracellular Ca2+ concentration rise and contraction. In recent years there have been several significant developments in our understanding of the signaling processes underlying mICAT generation. They have revealed important synergistic interactions between M2 and M3 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/InsP3/intracellular Ca2+ release system in the mI(CAT) physiological regulation.
Zholos
Alexander V
AV
Department of Physiology, Queen's University Belfast, Belfast, UK. a.zholos@qub.ac.uk
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009119:Muscle Contraction; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D050052:TRPC Cation Channels / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
D043585:Receptor, Muscarinic M2; D043562:Receptors, G-Protein-Coupled; D050052:TRPC Cation Channels; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D000109:Acetylcholine; D002118:Calcium