The Other (Muscarinic) Acetylcholine Receptors in Sympathetic Ganglia: Actions and Mechanisms
- 342 Downloads
Acetylcholine released from preganglionic sympathetic fibers can activate two types of acetylcholine receptors in sympathetic neurons, nicotinic and muscarinic. The former are ligand-gated ion channels responsible for direct synaptic transmission; the latter are G protein-coupled receptors that mediate various indirect modulatory effects. Most mammalian sympathetic neurons express three muscarinic receptor subtypes, M1, M2, and M4; some also express M3 receptors. Activation of M1 receptors stimulates the G protein Gq and causes a slow postsynaptic depolarization and an increase in the excitability, ultimately leading to an asynchronous action potential discharge, which can “break through” the nicotinic ganglion block. This is largely mediated by closure of voltage-gated K+ channels (the M channels) composed of Kv7.2 and Kv7.3 subunits and results from hydrolysis and depletion of membrane phosphatidylinositol-4,5-bisphosphate. Activation of M2 receptors hyperpolarizes and inhibits the postsynaptic neuron by opening G protein-gated inwardlyrectifying Kir K+ channels via the G protein Gi. M4 receptors inhibit N-type (CaV(2)) calcium channels via the G protein Go. In the postganglionic neuron somata, this enhances the excitability by reducing calcium-dependent potassium currents. Conversely, in postganglionic processes and axon terminals, CaV(2)-mediated inhibition reduces norepinephrine release and inhibits postganglionic transmission. Different muscarinic receptors may be anatomically segregated with their cognate G proteins and (in some cases) ion channels in signalling microdomains.
Keywordsacetylcholine muscarinic receptors ion channels G protein phosphatidylinositol-4 5-bisphosphate microdomain
Unable to display preview. Download preview PDF.
- 5.D. A. Brown, “The Skok legacy and beyond: molecular mechanisms of slow synaptic excitation in sympathetic ganglia,” Neurophysiology/Neurofiziologiya, 39, 284–289 (2007).Google Scholar
- 6.D. A. Brown and A. A. Selyanko, “Membrane currents underlying the slow excitatory post-synaptic potential in the rat sympathetic ganglion,” J. Physiol., 365, 335–364 (1985).Google Scholar
- 7.D. A. Brown, N. J. Buckley, M. P. Caulfield, et al., “Coupling of muscarinic acetylcholine receptors to neural ion channels: closure of K+ channels,” in: Molecular Mechanisms of Muscarinic Acetylcholine Receptor Function, J. Wess (ed.), R. G. Landes Comp., Austin, TX (1995), pp. 165–182.Google Scholar
- 26.D. A. Brown, “M Сurrents,” Ion Channels, Vol. 1, T. Narahashi (ed.), Plenum Press, New York (1988), pp. 55–99.Google Scholar
- 34.J. M. Fernandez-Fernandez, F. C. Abogadie, G. Milligan, et al., “Multiple pertussis toxin-sensitive G proteins can couple receptors to GIRK channels in rat sympathetic neurons when heterologously-expressed, but only native Gi proteins do so in situ,” Eur. J. Neurosci., 14, 283–292 (2001).PubMedCrossRefGoogle Scholar
- 41.J. Zhang. M. Bal, S. Bierbower, et al., “AKAP79/150 signal complexes in G-protein modulation of neuronal ion channels,” J. Neurosci., 31, 7199–7211 (2011).Google Scholar