RESEARCH
Acetylcholine is much more than the neurotransmitter described in usual textbooks
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This book presents an up-to-date review concerning acetylcholine, a messenger substance which is produced transiently in practically all living organisms, from bacteria to human beings. High acetylcholine concentrations have been encountered in growing parts of plants, in the royal jelly of bees, and in the human placenta. In vertebrates, many non-neuronal cells, such as epithelial cells, endothelial cells, immune cells or spermatozoids, secrete acetylcholine in response to specific signals.
Acetylcholine is better known as a neurotransmitter substance, supporting synaptic transmission in the central and autonomic nervous systems. Transmission in these places is a point-to-point process which is relatively rapid and shows many anatomical and physiological variations, according to synapses and animal species. Much more rapid is transmission in giant and specialised synapses, such as the neuromuscular junctions and their homologues, in the electric organs of certain fish. The mechanisms of acetylcholine release in these ultra-rapid junctions have been revisited in recent decades and the picture has completely changed.
As the book shows, acetylcholine signalling (also called cholinergic signalling) is of particular physiological and toxicological importance, since it can be perturbed by many natural or synthetic substances.
Link.to the book: https://www.cambridgescholars.com/product/978-1-5275-6721-4/
Yves Dunant, M.D.; Hon Professor at the Faculty of Medicine, Geneva. Medical activity in Switzerland and Kinshasa (Congo). Research carrier in Lausanne, Cambridge (UK), Paris and Geneva. Former Chairman and Professor of Pharmacology; President of the “Société Genevoise de Neuroscience”, Corresponding Member of the “Académie Royale de Médecine de Belgique”. Member of the International Society of Neurochemistry, of the Société des Neurosciences, etc.
Transmitter release in rapid synapses has been my constant thread since the sixties, starting with presynaptic recording, facilitation and LTP in the sympathetic ganglion (1). Then, we studied presynaptic mechanisms, mainly with the electric organ of Torpedo, as well as with SNC synapses, often in collaboration with Maurice Israël et al. (France). Selected milestones: Acetylcholine is synthesised in the cytosol of nerve terminals and slowly transported into vesicles. On nerve stimulation, cytosolic ACh is used and renewed before vesicular ACh, which behaves as a reserve compartment for neurotransmitter and ATP (2,3). Transmission is quantal in electric organ like in NM junction. One quantum arises from synchronous release of 7-10’000 ACh molecules; it is composed of subunits of ~1’000 ACh molecules. The content of a synaptic vesicle (100-200’000 ACh molecules) is much larger (4). Transmission of a single nerve impulse is accompanied by the fleeting occurrence (2 ms duration) of large intramembrane particles in the presynaptic membrane (5). Ca2+-dependent and quantal transmitter release is supported by mediatophore, a proteolipid homo-oligomer present at the presynaptic active zones (6,7). The presynaptic action potential triggers a very brief “Ca2+ spark” in the active zone. Ca2+ is then quickly buffered by a vesicular Ca2+/H+-antiport requiring synaptotagmin-1, and more slowly by several others processes. (7,8). In synaptic vesicles, calcium binds to a gel matrix in exchange for neurotransmitter and ATP. Calcium is eventually expelled, most probably by exocytosis (8,9). Ultra-fast and slow cholinergic transmission are characterized by different acetylcholinesterase molecular forms (10).
1- Dunant, Y. (1972) J. Physiol. Lond. 221, 577-87.
2- Dunant, Y. & Israël, M. (1985) Sci. Amer. 252, 58-66.
3- Dunant, Y. (1986) Prog. Neurobiol. 26, 55-92.
4- Girod, R., et al. (1993) J. Physiol. Lond. 471, 129-57.
5- Muller, D., et al. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 590-94.
6- Falk-Vairant, J. et al. (1996) Proc. Natl. Acad. Sci. USA 93, 5203-207.
7- Dunant, Y. & Israël, M. (2000) Biochimie 82, 289-302.
8- Cordeiro, J. M. (2011) J. Physiol 589, 149-167 ; (2013) J. Neurochem. 126, 36-46.
9- Dunant, Y., et al. (2009) Ann. N. Y. Acad. Sci. 1152, 100-112 ; (2014)
10-.Dunant , Y. and Gisiger, V. (2017) Molecules 22, 1300-1316.
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Ultrafast and Slow Cholinergic Transmission.
Different Involvement of Acetylcholinesterase
Molecular Forms
Yves Dunant and Victor Gisiger
Pour fêter mes 80 ans, j’ai écrit cette petite revue cholinergique qui est en train de faire un tabac s’il faut en croire le nombre de lecture et de tirages sur internet ! Je l’ai écrite avec un ancien copain de Lausanne, Victor Gisiger, qui est depuis longtemps au Canada où il continue à travailler à la retraite comme bénévole car il estime que l’enseignement de l’anatomie est négligé dans leurs programme alors que les étudiants en médecine en ont un terrible besoin. Ses travaux sur l’acétylcholinestérase extra-synaptique dérangeaient les ténors à l’époque, tout comme les nôtres sur la libération de ce neurotransmetteur. C’est le moment de remettre l’église au milieu du village.
Amicalement
Yves
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Transmitter release in rapid synapses has been my constant thread since the sixties, starting with presynaptic recording, facilitation and LTP in sympathetic ganglion (1). Then, we studied presynaptic mechanisms, mainly with the electric organ of Torpedo, as well as with SNC synapses, often in collaboration with Maurice Israël et al. (France). Selected milestones: Acetylcholine is synthesised in the cytosol of nerve terminals and slowly transported into vesicles. On nerve stimulation, cytosolic ACh is used and renewed before vesicular ACh, which behaves as a reserve compartment for neurotransmitter and ATP (2). Transmission is quantal in electric organ like in NM junction. One quantum arises from synchronous release of 7-10’000 ACh molecules; it is composed of subunits of ~1’000 ACh molecules. The content of a synaptic vesicle (100-200’000 ACh molecules) is much larger (3). Desynchronized release of quantal subunits is prominent under conditions when the energy supply is impaired or when presynaptic proteins are damaged, for instance by clostridial toxins (4). Transmission of a single nerve impulse is accompanied by the fleeting occurrence (2 ms duration) of large intramembrane particles in the presynaptic membrane (5). Ca2+-dependent and quantal transmitter release is supported by mediatophore, a proteolipid homo-oligomer present at the presynaptic active zones (6). The presynaptic action potential triggers a very brief “Ca2+ spark” in the active zone. Ca2+ is then quickly buffered by a vesicular Ca2+/H+-antiport requiring synaptotagmin-1, and more slowly by several others processes (7). In synaptic vesicles, calcium binds to a gel matrix in exchange for neurotransmitter and ATP. Calcium is eventually expelled, most probably by exocytosis (8,9).