![]() Linked to 2nd messenger systems through G proteins (see below) Nicotinic and Muscarinic Receptors and their Actions Table I summarizes some of the properties of nicotinic and muscarinic receptors. This classification is based on two chemical agents that mimic the effects of ACh at the receptor site nicotine and muscarine. There are two broad classes of cholinergic receptors: nicotinic and muscarinic. ![]() This proximity implies the two important cholinergic proteins are probably regulated coordinately.Ĭa 2+-dependent ACh secretion and two toxins that modify secretion. Interestingly, the gene for VAChT is contained on the first intron of the choline acetyltransferase gene. No useful pharmacological agents are available to modify cholinergic function through interaction with the storage of ACh. The acidified vesicle then uses a vesicular ACh transporter (VAChT) to exchange protons for ACh molecules. The uptake of ACh into storage vesicle occurs through an energy-dependent pump that acidifies the vesicle. Vesicle-bound ACh is not accessible to degradation by acetylcholinesterase (see below). ![]() A small amount is also free in the cytosol. The majority of the ACh in nerve endings is contained in clear (as viewed in the electron microscope) 100 um vesicles. However, this has not been effective, probably because the administration of choline does not increase the availability of choline in the CNS. One of the strategies to increase ACh neurotransmission is the administration of choline in the diet. Another source is the breakdown of the phospholipid, phosphatidylcholine. Consequently much of the choline used for ACh synthesis comes from the recycling of choline from metabolized ACh. As will be described later, the inactivation of ACh is converted by metabolism to choline and acetic acid. Ca 2+ appears to be involved in both of these regulatory mechanisms. During increased neuronal activity the availability of acetyl-CoA from the mitochondria is upregulated as is the uptake of choline into the nerve ending from the synaptic cleft. The rate-limiting steps in ACh synthesis are the availability of choline and acetyl-CoA. The presence of CAT is the "marker" that a neuron is cholinergic, only cholinergic neurons contain CAT. Both CAT and ACh may be found throughout the neuron, but their highest concentration is in axon terminals. As is the case for all nerve terminal proteins, CAT is produced in the cholinergic cell body and transported down the axon to the nerve endings. Click on the region of the cell describing these processes to learn more about each one.ĭiagram showing the role of acetyl-CoA from glucose metabolism and choline from the high affinity uptake in ACh biosynthesis.Ĭholine acetyltransferase (CAT): As shown in Figure 11.5, ACh is synthesized by a single step reaction catalyzed by the biosynthetic enzyme choline acetyltransferase. ![]() Most subcortical areas are innervated by neurons from the ponto-mesencephalic region (purple in Figure 11.3).ġ1.5 Introduction to the Cell Biology of the Cholinergic Synapseįigure 11.4 is a summary of the biological mechanisms involved in the synthesis, storage secretion, receptor interaction and termination of acetylcholine. There is also a projection from the medial septal and diagonal band region to limbic structures (blue). Degeneration of this pathway is one of the pathologies associated with Alzheimer's disease. Noteworthy is the cholinergic projection from the nucleus basalis of Meynert (in the basal forebrain) to the forebrain neocortex and associated limbic structures, represented by the black pathway in Figure 11.3. A few important long-axon cholinergic pathways have also been identified. In the central nervous system, ACh is found primarily in interneurons, shown in Figure 11.3 as orange and green cell clusters. Distribution of cholinergic cell groups and projections in the rat brain. ![]()
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