Journal of Molecular Neuroscience

, Volume 41, Issue 3, pp 340–346 | Cite as

Muscarinic Acetylcholine Receptors (mAChRs) in the Nervous System: Some Functions and Mechanisms

  • David A. BrownEmail author


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 M1/M3/M5 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 M2 or M4 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.


Acetylcholine Muscarinic receptors G proteins Potassium channels Calcium channels Corelease 



Work from the author’s laboratory was supported by the U.K. Medical Research Council and the Wellcome Trust.


  1. Allen TG (1997) The ‘sniffer-patch’ technique for detection of neurotransmitter release. Trends Neurosci 20:192–197CrossRefPubMedGoogle Scholar
  2. Allen TG (1999) The role of N-, Q- and R-type Ca2+ channels in feedback inhibition of ACh release from rat basal forebrain neurones. J Physiol 515:93–107CrossRefPubMedGoogle Scholar
  3. Allen TG, Brown DA (1993) M2 muscarinic receptor-mediated inhibition of the Ca2+ current in rat magnocellular cholinergic basal forebrain neurones. J Physiol 466:173–189PubMedGoogle Scholar
  4. Allen TGJ, Brown DA (1996) Detection and modulation of acetylcholine release from neurites of rat-cultured basal forebrain cells. J Physiol 492:453–466PubMedGoogle Scholar
  5. Allen TG, Abogadie FC, Brown DA (2006) Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic” basal forebrain neurons. J Neurosci 26:1588–1595CrossRefPubMedGoogle Scholar
  6. Benardo LS (1993) Characterization of cholinergic and noradrenergic slow excitatory postsynaptic potentials from rat cerebral cortical neurons. Neuroscience 53:11–22CrossRefPubMedGoogle Scholar
  7. Bernheim L, Mathie A, Hille B (1992) Characterization of muscarinic receptor subtypes inhibiting Ca2+ current and M current in rat sympathetic neurons. Proc Natl Acad Sci USA 89:9544–9548CrossRefPubMedGoogle Scholar
  8. Blackmer T, Larsen EC, Takahashi M et al (2001) G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry. Science 292:293–297CrossRefPubMedGoogle Scholar
  9. Broicher T, Wettschureck N, Munsch T et al (2008) Muscarinic ACh receptor-mediated control of thalamic activity via G(q)/G (11)-family G-proteins. Pflugers Arch 456:1049–1060Google Scholar
  10. Brown DA, Adams PR (1980) Muscarinic suppression of a novel voltage-sensitive K+-current in a vertebrate neurone. Nature 283:673–676CrossRefPubMedGoogle Scholar
  11. Brown DA, Selyanko AA (1985) Membrane currents underlying the slow excitatory post-synaptic potential in the rat sympathetic ganglion. J Physiol 365:335–364Google Scholar
  12. Brown DA, Abogadie FC, Allen TG, Buckley NJ, Caulfield MP, Delmas P, Haley JE, Lamas JA, Selyanko AA (1997) Muscarinic mechanisms in nerve cells. Life Sci 60:1137–1144CrossRefPubMedGoogle Scholar
  13. Brown DA, Hughes SA, Marsh SJ, Tinker A (2007) Regulation of M(Kv7.2/7.3) channels in neurons by PIP(2) and products of PIP(2) hydrolysis: significance for receptor-mediated inhibition. J Physiol 582:917–925CrossRefPubMedGoogle Scholar
  14. Caulfield MP (1993) Muscarinic receptors—characterization, coupling and function. Pharmacol Ther 58:319–379CrossRefPubMedGoogle Scholar
  15. Caulfield MP, Birdsall NJ (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50:279–290PubMedGoogle Scholar
  16. Chen S, Yaari Y (2008) Spike Ca2+ influx upmodulates the spike afterdepolarization and bursting via intracellular inhibition of KV7/M channels. J Physiol 586:1351–1363CrossRefPubMedGoogle Scholar
  17. Cole AE, Nicoll RA (1984) Characterization of a slow cholinergic post-synaptic potential recorded in vitro from rat hippocampal pyramidal cells. J Physiol 352:173–188PubMedGoogle Scholar
  18. Dale HH (1914) The action of certain esters and ethers of choline, and their relation to muscarine. J Pharmacol Exp Ther 6:147–190Google Scholar
  19. Delmas P, Abogadie FC, Dayrell M, Haley JE, Milligan G, Caulfield MP, Brown DA, Buckley NJ (1998) G-proteins and G-protein subunits mediating cholinergic inhibition of N-type calcium currents in sympathetic neurons. Eur J Neurosci 10:1654–1666CrossRefPubMedGoogle Scholar
  20. Dodd J, Horn JP (1983) Muscarinic inhibition of sympathetic C neurones in the bullfrog. J Physiol 334:271–291PubMedGoogle Scholar
  21. Dudar JD, Szerb JC (1969) The effect of topically applied atropine on resting and evoked cortical acetylcholine release. J Physiol 203:741–762PubMedGoogle Scholar
  22. Egan TM, North RA (1986) Acetylcholine hyperpolarizes central neurones by acting on an M2 muscarinic receptor. Nature 319:405–407CrossRefPubMedGoogle Scholar
  23. Fernandez-Fernandez JM, Wanaverbecq N, Halley P, Caulfield MP, Brown DA (1999) Selective activation of heterologously expressed G protein-gated K+ channels by M2 muscarinic receptors in rat sympathetic neurones. J Physiol 515:631–637CrossRefPubMedGoogle Scholar
  24. Fernández-Fernández JM, Abogadie FC, Milligan G, Delmas P, Brown DA (2001) Multiple pertussis toxin-sensitive G-proteins can couple receptors to GIRK channels in rat sympathetic neurons when expressed heterologously, but only native G(i)-proteins do so in situ. Eur J Neurosci 14:283–292CrossRefPubMedGoogle Scholar
  25. Gahwiler BH, Brown DA (1985) Functional innervation of cultured hippocampal neurones by cholinergic afferents from co-cultured septal explants. Nature 313:577–579CrossRefPubMedGoogle Scholar
  26. Gamper N, Shapiro MS (2007) Regulation of ion transport proteins by membrane phosphoinositides. Nat Rev Neurosci 8:921–934CrossRefPubMedGoogle Scholar
  27. Halliwell JV, Adams PR (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res 250:71–92CrossRefPubMedGoogle Scholar
  28. Hassall CJ, Stanford SC, Burnstock G, Buckley NJ (1993) Co-expression of four muscarinic receptor genes by the intrinsic neurons of the rat and guinea pig heart. Neuroscience 56:1041–1048CrossRefPubMedGoogle Scholar
  29. Hulme EC, Birdsall NJ, Buckley NJ (1990) Muscarinic receptor subtypes. Annu Rev Pharmacol Toxicol 30:633–673CrossRefPubMedGoogle Scholar
  30. Kuba K, Koketsu K (1978) Synaptic events in sympathetic ganglia. Prog Neurobiol 11:77–169CrossRefPubMedGoogle Scholar
  31. Lu B, Su Y, Das S, Wang H, Wang Y, Liu J, Ren D (2009) Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature 457:741–744Google Scholar
  32. McCormick DA, Prince DA (1986) Acetylcholine induces burst firing in thalamic reticular neurones by activating a potassium conductance. Nature 319:402–405CrossRefPubMedGoogle Scholar
  33. McCormick DA, Williamson A (1989) Convergence and divergence of neurotransmitter action in human cerebral cortex. Proc Natl Acad Sci USA 86:8098–8102CrossRefPubMedGoogle Scholar
  34. Nicoll RA (1985) The septo-hippocampal projection: a model cholinergic pathway. Trends Neurosci 8:533–536CrossRefGoogle Scholar
  35. Shah MM, Migliore M, Valencia I, Cooper EC, Brown DA (2008) Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci USA 105:7869–7874CrossRefPubMedGoogle Scholar
  36. Shapiro MS, Loose MD, Hamilton SE, Nathanson NM, Gomeza J, Wess J, Hille B (1999) Assignment of muscarinic receptor subtypes mediating G-protein modulation of Ca(2+) channels by using knockout mice. Proc Natl Acad Sci USA 96:10899–10904CrossRefPubMedGoogle Scholar
  37. Shen W, Hamilton SE, Nathanson NM, Surmeier DJ (2005) Cholinergic suppression of KCNQ channel currents enhances excitability of striatal medium spiny neurons. J Neurosci 25:7449–7458CrossRefPubMedGoogle Scholar
  38. Suh BC, Hille B (2005) Regulation of ion channels by phosphatidylinositol 4, 5-bisphosphate. Curr Opin Neurobiol 15:370–378CrossRefPubMedGoogle Scholar
  39. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282:1890–1893CrossRefPubMedGoogle Scholar
  40. Wickman K, Clapham DE (1995) Ion channel regulation by G proteins. Physiol Rev 75:865–885PubMedGoogle Scholar
  41. Zaika O, Lara LS, Gamper N, Hilgemann DW, Jaffe DB, Shapiro MS (2006) Angiotensin-II regulates neuronal excitability via PIP2-dependent modulation of Kv7 (M-type) potassium channels. J Physiol 575:49–67CrossRefPubMedGoogle Scholar
  42. Zhang W, Basile AS, Gomeza J, Volpicelli LA, Levey AI, Wess J (2002) Characterization of central inhibitory muscarinic autoreceptors by the use of muscarinic acetylcholine receptor knock-out mice. J Neurosci 22:1709–1717PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Neuroscience, Physiology and PharmacologyUniversity College LondonLondonUK

Personalised recommendations