BIOSYNTHESIS OF ACETYLCHOLINE IN CNS AND CHOLINERGIC TRANSMISSION
1. BIOSYNTHESIS OF
ACETYLCHOLINE IN CNS AND
CHOLINERGIC TRANSMISSION
BY
ADESEJI, WASIU ADEBAYO (B.Sc Hons)
08/46KA006
ANA 808: ADVANCED NEURONATOMY
DEPARTMENT OF ANATOMY,
UNIVERSITY OF ILORIN.
JULY, 2015.
Lecturer: DR O. B. AKINOLA (P.hd)
3. INTRODUCTION
Acetylcholine (ACh), the first
neurotransmitter discovered, was
originally described as "vagus stuff"
by Otto Loewi because of its ability
to mimic the electrical stimulation of
the vagus nerve.
It is now known to be a
neurotransmitter at all autonomic
ganglia, at many autonomically
innervated organs, at the
neuromuscular junction, and at many
synapses in the CNS.
Ach is a small-molecule excitatory
neurotransmitter with a wide variety
of known functions
Within the central nervous system
(CNS), cholinergic cells (neurons that
use ACh as a neurotransmitter) are
found in several different locations
of the brain, including the striatal 3
7. Depending on which area of the brain it is found in, ACh may
be involved in any one of several different functions. Some of
these functions include the conduction of pain, the regulation of
neuroendocrine function, the regulation of REM sleep cycles, and
the process of learning and memory formation.
Within the basal forebrain, it is the cholinergic cells of the
septal nuclei that play a large role in learning and memory.
These neurons send major projections to the hippocampus, a
structure particularly important for the normal formation of
declarative memories. Several noteworthy clinical cases have
shown that lesions in this area of the brain alone can greatly
impair an individual's ability to form new declarative memories.
It is this cholinergic system, among others, that has been shown
to suffer serious neurodegeneration in Alzheimer's disease, a
condition characterized by a significant failure of memory and
other cognitive functions.
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9. SYNTHESIS
OF ACHACh is made up of choline and acetate. These precursors
must be readily available to the neuron terminal at all
times so that ACh can be synthesized whenever it is
needed.
Choline is a compound that can be obtained from foods
such as egg yolks, kidney, liver, seeds, legumes, and
various vegetables. It is also naturally produced by the
liver. Free choline circulating in blood plasma readily
crosses the blood-brain barrier and is taken up by
cholinergic nerve terminals, for the most part, by a high-
affinity choline uptake (HACU) system that is
temperature-, energy- and sodium-dependent.
The rate-limiting steps in ACh synthesis are the
availability of choline and acetyl-CoA. 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. Ca2+9
10. SYNTHESIS
OF ACH
ACh is an example of an excitatory small-molecule
neurotransmitter.
Small-molecule neurotransmitters are synthesized
locally within the axon terminal.
The synthesis of ACh requires the enzyme choline
actyltransferase and, like all small-molecule
neurotransmitters, takes place within the nerve terminal.
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12. CHOLINERGIC
TRANSMISSION
1)When the nerve impulse (Action potential) moves down the presynaptic axon
to the terminal bulb the change in the membrane action potential causes the
opening of voltage gated calcium channels open allowing Ca2+ ions to pass from
the synaptic cleft into the axon bulb.
2) Within the bulb the increase
in Ca2+ concentration causes the
synaptic vesicles that contain
acetylcholine to fuse with the
axonal membrane and open
spilling their contents into
the synaptic cleft.
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13. CHOLINERGIC
TRANSMISSIONThe postsynaptic membrane of the receptor dendrite has
specific cholinergic receptors toward which the
neurotransmitter diffuses. Binding of acetylcholine trigger the
opening of ion channels in the postsynaptic membrane initiating
action potential that can pass in the next axon.
Acetylcholine receptors:
Acetylcholine receptors are ion channels receptors made of
many subunits arranged in the form [(α2)(β)(γ)(δ)].
When Acetylcholine is not bounded to the receptors, the bulky
hydrophobic leu side close the central channels preventing the
diffusion of any ions.
Binding of two acetylcholine molecules to the receptors will
rotate the subunits in which the smaller polar residues will line
the ion channel causing the influx of Na+ into the cell and
efflux of K+ resulting in a depolarization of the postsynaptic
neuron and the initiation of new action potential.
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16. MUSCARINIC RECEPTOR
Features M1 M2 M3
Location Autonomic and enteric
ganglia
Paracrine cell gastric
gland
CNS
SA node , AV node ,
presynaptic terminal
Exocrine gland ,
smooth muscle ,
vascular
endothelium
Function Gastric acid
Cns excitation
Gi motility
Dercrase rate of impulse
generation
Velocity of conduction
Bradycardia
contractility
Increase in exocrine
secretion , smooth
muscle contraction
Mechanism ip3 , DAG ,
increase in ca 2+ conc.
Inhibition of adenyl
cyclase
, decrease CAMP
opening of k+ channel
Same as the M1
receptor
Agonist Oxotremorine Methacholine Bethacholine
Antagonist Pirenzepine
Telenzepine
Triptramine Tolterodine
Darifenacin
17. Eyes: contraction of ciliary muscle and smooth muscle of
the iris sphincter (miosis)
Heart : Bradycardia (possibly preceded by tachycardia),
decrease force of conytraction
Blood vessel : vasodilation ( EDRF)
Lung : bronchoconstriction and increase secretion
Pancreas : increased pancreatic juice
Urinary bladder : voiding of urine ( detrusor and spincter)
Sweat gland : increased sweating
ACETYLCHOLINE –
MUSCARINIC ACTION
18. ACETYCHOLINE : NICOTINIC
ACTION
Neuro-muscular Junction: nicotinic Nm receptor
Stimulation lead to muscle contraction
Sympathetic And P. Sympathetic Ganglia: Nn receptor
Release of NE and Ach
Adrenal Medulla : Nn receptor
Release of adrenaline