Some Currently Neglected Aspects of Cholinergic Function

Abstract

At the request of the organizers of the XIII International Symposium on Cholinergic Mechanisms, I have selected for review three topics not well represented at the meeting: the synthesis, storage, and release of acetylcholine at cholinergic nerve endings; cholinergic-specific antigens; and neuropeptides as cholinergic co-transmitters. The first topic is illustrated by work with two model systems, the electromotor nerve terminals of the electric ray and the myenteric plexus of the guinea-pig ileum, the second by work with Chol-1, a group of cholinergic-specific gangliosides sialylated on their N-acetylgalactosamine residues, and the third by vasoactive intestinal polypeptide which is a co-transmitter at 70% of cholinergic nerve endings in brain and is also present in both of the model cholinergic systems.

Frank Beach Award Winner: Steroids as neuromodulators of brain circuits and behavior

“…Most neuropeptides are co-released with ordinary fast-acting neurotransmitters, which means that their downstream effects are very likely inter-dependent (Dabrowska et al, 2013; Dicken et al, 2012; Whittaker, 2010). In fact the co-release of neuropeptide Y and GABA in hypothalamic neurons is necessary for the postsynaptic effects of either to take place (van den Pol, 2012).…”

Synaptic Soluble and Membrane-Bound Choline Acetyltransferase as a Marker of Cholinergic Function In Vitro and In Vivo

“…It is necessary to understand the true mechanisms of the regulation, maintenance and recovery of brain functions. It should be noted that studies on synaptic fraction levels were carried out along these lines from the beginning [4,18,[21][22][23][24][25][26][27][28][29][30][31].…”

“…ACh is an ester of acetic acid and choline with the chemical formula CH 3 COO(CH 2 ) 2 N+ (CH 3 ) 3 and systematic name 2-acetoxy-N,N,N-trimethylethanaminium.The cycle of ACh synthesis, storage, release and degradation has been well-characterized at the cellular and molecular levels [26,35,36]. Briefly (Figure 2), ACh is synthesized in the cytoplasm of cholinergic neurons from the precursors choline and acetyl-coenzyme A by the enzyme choline acetyltransferase (ChAT), and is then taken up into synaptic vesicles for storage by the vesicular acetylcholine transporter (VAChT).…”

“…Depolarization of the nerve terminal causes the fusion of synaptic vesicles with the presynaptic membrane at specialized release sites called active zones (named the junction complex in the subsynaptic fraction). Depositing and releasing ACh is a calcium-dependent process that involves the coordinated actions of many presynaptic proteins [26,37]. When vesicles are linked up with the presynaptic membrane, ACh diffuses into the synaptic cleft where it can bind to subtypes of nicotinic and muscarinic receptors located on both post-and presynaptic membranes.…”

The mechanisms and possible sites of acetylcholine release during chick primary sensory neuron differentiation

“…In addition to the classical ACh release mechanism, which is characterized by ACh transport and accumulation in vesicles that subsequently fuse with the plasma membrane (Whittaker, 1988(Whittaker, , 2010, a second release mechanism that is mediated by mediatophore, a transmembrane protein responsible for the direct translocation of ACh across the plasma membrane, was described by Israel and Dunant (1999). Although DRG neurons express the ACh vesicular transporter (VAChT) , our results demonstrate that ACh release is not confined to nerve endings (see above) where vesicle accumulation is expected, suggesting that mediatophore might play a role in ACh release along the growing fibers of DRG neurons.…”