Chapter 7: Acetylcholine Flashcards
Where are cholinergic neurons located?
In the peripheral nervous system (including neuromuscular joints) and at specific synapses within the sympathetic and parasympathetic nervous divisions of the autonomic nervous system.
How is acetylcholine synthesized?
Acetylcholine is synthesized from the precursors choline and acetyl coenzyme A. Choline comes from dietary fats and can also be produced in the liver. Acetyl coenzye A is made in all cells by the metabolism of sugars and fats. The enzyme choline acetyltransferase catalyzes the synthesis and transfers the acetyl group from acetyl coenzyme A to choline to make acetylcholine. The second product of this reaction is coenzyme A.
What controls the rate of acetylcholine synthesis?
- availability of precursors
2. rate of cell firing
How is acetylcholine inactivated?
Acetylcholine is inactivated by the enzyme acetylcholinesterase.
Where is the enzyme acetylcholinesterase (AChE) present?
- inside the presynaptic cell
- on the membrane of the postsynaptic cell
- at neuromuscular junctions
What does AChE do in the presynaptic cell?
metabolizes excess acetylcholine when too much is synthesized
What does AChE do on the membrane of the postsynaptic cell?
metabolizes molecules that have been released into the synaptic cleft
What does AChE do at neuromuscular junctions?
breaks down acetylcholine quickly after it causes a muscle contraction so that the muscle can relax and contract again
What are the products of acetylcholine breakdown?
- choline
2. acetic acid
Describe the anatomy of the cholinergic pathway in the parasympathetic branch of the autonomic nervous system.
In the parasympathetic branch, cholinergic preganglionic neurons send their axons to cholinergic ganglionic neurons which in turn send their axons to the target organ and release acetylcholine.
Describe the anatomy of the cholinergic pathway in the sympathetic branch of the autonomic nervous system.
In the sympathetic branch, cholinergic preganglionic neurons send their axons to cholinergic ganglionic neurons which in turn send their axons to the target organ and release norepinephrine.
Describe the anatomy of the cholinergic pathways in the brain.
- Cholinergic neurons in the basal forebrain cholinergic system (BFCS) innervate the cerebral cortex, hippocampus, amygdala and limbic system.
- Cholinergic neurons in the laterodorsal tegmental nuclei innervate the ventral tegmental area.
- Cholinergic cells in the pedunclopontine tegmental nuclei innervate the substantia nigra.
What are the cholinergic receptor subtypes?
- nicotinic receptors
2. muscarinic receptors
Where are nicotinic receptors located?
- muscle cells at neuromuscular junctions
- ganglionic neurons in the sympathetic and parasympathetic systems
- some neurons in the brain.
Describe how nicotonic receptors work.
Nicotinic receptors are ionotropic and are made up of five subunits arranged to form a channel. When acetylcholine binds to the receptor the ionic channel opens and sodium (Na+) and calcium (Ca2+) ions enter the cell producing a fast excitatory response. The excitatory response happens because of depolarization of the cell membrane. In the brain the neuron is more likely to fire and in a muscle cell it will respond to this depolarization by contracting. Thus, they mediate fast excitatory responses in both the CNS and PNS.
How do nicotinic receptors work in the brain?
They are presynaptic and postsynaptic. Presynaptic nicotinic receptors enhance neurotransmitter release from nerve terminals. Postsynaptic receptors stimulate cell firing.
Where are muscarinic receptors located?
- widely distriuted in the brain and are concentrated in the forebrain, neocortex, hippocampus, thalamus, and striatum
- the cardiac muscle of the heart (M2 receptors)
- smooth muscles of organs like the stomach and intestines
- secretory glands like the salivary glands (M3 receptors)
Describe how muscatinic receptors work.
Muscarinic receptors are metabotropic and there are five different types designated M1 through M5. They operate through activation of the phosphoinositide second-messenger system, inhibition of cAMP synthesis, and stimulation of K+ channel opening.
How is acetylcholine loaded into synaptic vesicles?
By a transport protein in the vesicle membrane called the vesicular acetylcholine transporter (VAChT).
What happens to the choline from acetylcholine breakdown?
Much of it is taken back up into the cholinergic nerve terminal by a choline transporter that plays a critical role in maintaining ongoing ACh synthesis.
What are some uses of acetylcholinesterase (AChE) antagonists (blockers)?
- drugs for Alzheimer’s disease
- insecticides
- nerve gases
How are nicotinic receptors in neurons and muscles different?
They have different subunits which leads to significant pharmacological differences. Muscle nicotinic receptors have two ACh binding sites and both must be occupied for the channel to open.
What three states can ionotropic receptors exist in?
- Closed
- Open
- Desensitized
What does it mean if a receptor is in a desensitized state?
There is a lack of response to an agonist where the channel is closed and cannot be opened despite presence of the agonist. The rate of receptor conversion to a desensitized state is enhanced by prolonged exposure to an agonist.
What does it mean if a receptor undergoes resensitization?
The receptor was desensitized but there has been a return of functioning and there is a normal response to agonist stimulation.
What is depolarization block?
Process in which the resting potential across the cell membrane is lost and the cell is inable to generate action potentials. The neuron cannot be excited until the membane is repolarized.
