Muscarinic cationic current in gastrointestinal smooth muscles: signal transduction and role in contraction.
1 The muscarinic receptor plays a key role in the parasympathetic nervous control of various peripheral tissues including gastrointestinal tract. The neurotransmitter acetylcholine, via activating muscarinic receptors that exist in smooth muscle, produces its contraction. 2 There is the opening of cationic channels as an underlying mechanism. The opening of cationic channels results in influxes of Ca2+ via the channels into the cell and also via voltage-dependent Ca2+ channels which secondarily opened in response to the depolarization, providing an amount of Ca2+ for activation of the contractile proteins. 3 Electrophysiological and pharmacological studies have shown that the cationic channels as well as muscarinic receptors exist in many visceral smooth muscle cells. However, the activation mechanisms of the cationic channels are still unclear. 4 In this article, we summarize the current knowledge of the muscarinic receptor-operated cationic channels, focusing on the receptor subtype, G protein and other signalling molecules that are involved in activation of these channels and on the molecular characteristics of the channel. This will improve strategies aimed at developing new selective pharmacological agents and understanding the activation mechanism and functions of these channels in physiological systems.
Unno
T
T
Laboratory of Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Gifu 501-1193, Japan.
Matsuyama
H
H
Okamoto
H
H
Sakamoto
T
T
Yamamoto
M
M
Tanahashi
Y
Y
Yan
H-D
HD
Komori
S
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling; D019204:GTP-Binding Proteins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000294:innervation / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D011976:Receptors, Muscarinic; D050052:TRPC Cation Channels; D011505:Protein-Tyrosine Kinases; D009219:Myosin-Light-Chain Kinase; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000109:Acetylcholine