Muscarinic acetylcholine receptors (mAChRs) in the nervous system: some functions and mechanisms.
This article summarizes some of the effects of stimulating muscarinic receptors on nerve cell activity as observed by recording from single nerve cells and cholinergic synapses in the peripheral and central nervous sytems. It addresses the nature of the muscarinic receptor(s) involved and the ion channels and subcellular mechanisms responsible for the effects. The article concentrates on three effects: postsynaptic excitation, postsynaptic inhibition, and presynaptic (auto) inhibition. Postsynaptic excitation results primarily from the inhibition of potassium currents by M(1)/M(3)/M(5) receptors, consequent upon activation of phospholipase C by the G protein Gq. Postsynaptic inhibition results from M2-activation of inward rectifier potassium channels, consequent upon activation of Gi. Presynaptic inhibition results from M(2) or M(4) inhibition of voltage-gated calcium channels, consequent upon activation of Go. The segregation receptors, G proteins and ion channels, and the corelease of acetylcholine and glutamate from cholinergic fibres in the brain are also discussed.
Brown
David A
DA
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E6BT, UK. d.a.brown@ucl.ac.uk
D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017933:Peripheral Nervous System / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic / Q000379:methods
D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins
Pharmacol Rev. 1998 Jun;50(2):279-90
9647869
J Physiol. 2006 Aug 15;575(Pt 1):49-67
16777936
Nature. 1980 Feb 14;283(5748):673-6
6965523
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9544-8
1329101
Brain Res. 1982 Oct 28;250(1):71-92
6128061
J Physiol. 1999 Feb 15;515 ( Pt 1):93-107
9925881
Eur J Neurosci. 2001 Jul;14(2):283-92
11553279
Physiol Rev. 1995 Oct;75(4):865-85
7480165
Nature. 1986 Jan 30-Feb 5;319(6052):405-7
2418362
J Physiol. 2008 Mar 1;586(5):1351-63
18187471
Nature. 1985 Feb 14-20;313(6003):577-9
3969160
J Physiol. 1993 Jul;466:173-89
8410690
J Neurosci. 2005 Aug 10;25(32):7449-58
16093396
J Physiol. 1984 Jul;352:173-88
6747887
Nat Rev Neurosci. 2007 Dec;8(12):921-34
17971783
Neuroscience. 1993 Oct;56(4):1041-8
8284034
J Physiol. 1999 Mar 15;515 ( Pt 3):631-7
10066893
Curr Opin Neurobiol. 2005 Jun;15(3):370-8
15922587
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7869-74
18515424
Life Sci. 1997;60(13-14):1137-44
9121358
J Neurosci. 2006 Feb 1;26(5):1588-95
16452682
Nature. 1986 Jan 30-Feb 5;319(6052):402-5
2418361
Eur J Neurosci. 1998 May;10(5):1654-66
9751138
Prog Neurobiol. 1978;11(2):77-169
33420
Nature. 2009 Feb 5;457(7230):741-4
19092807
Pflugers Arch. 2008 Sep;456(6):1049-60
18350314
J Neurosci. 2002 Mar 1;22(5):1709-17
11880500
Science. 2001 Apr 13;292(5515):293-7
11303105
Annu Rev Pharmacol Toxicol. 1990;30:633-73
2188581
Trends Neurosci. 1997 May;20(5):192-7
9141193
J Physiol. 1985 Aug;365:365-87
2411921
J Physiol. 2007 Aug 1;582(Pt 3):917-25
17395626
J Physiol. 1969 Aug;203(3):741-62
5387031
Science. 1998 Dec 4;282(5395):1890-3
9836639
J Physiol. 1983 Jan;334:271-91
6602878
Pharmacol Ther. 1993 Jun;58(3):319-79
7504306
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10899-904
10485923
Neuroscience. 1993 Mar;53(1):11-22
8385746
J Physiol. 1996 Apr 15;492 ( Pt 2):453-66
9019542
Proc Natl Acad Sci U S A. 1989 Oct;86(20):8098-102
2573061