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Questions and Answers
What role do cholinesterases play in cholinergic transmission?
What role do cholinesterases play in cholinergic transmission?
What is the role of the pre-synaptic neuron?
What is the role of the pre-synaptic neuron?
Which of the following statements about neurotransmitter actions is correct?
Which of the following statements about neurotransmitter actions is correct?
What type of synapse is characterized by a gap junction?
What type of synapse is characterized by a gap junction?
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What is the primary effect of anticholinesterases like neostigmine?
What is the primary effect of anticholinesterases like neostigmine?
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Which of the following statements about electrical synapses is true?
Which of the following statements about electrical synapses is true?
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What distinguishes muscarinic from nicotinic actions?
What distinguishes muscarinic from nicotinic actions?
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Which neurotransmitter is associated with cholinergic transmission?
Which neurotransmitter is associated with cholinergic transmission?
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Which of the following is true regarding the recycling of choline?
Which of the following is true regarding the recycling of choline?
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How do chemical synapses conduct signals compared to electrical synapses?
How do chemical synapses conduct signals compared to electrical synapses?
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What characteristic is NOT typical of chemical synapses?
What characteristic is NOT typical of chemical synapses?
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Which of the following best describes the synaptic cleft?
Which of the following best describes the synaptic cleft?
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In which scenario would you expect to see fatigue occurring?
In which scenario would you expect to see fatigue occurring?
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Which type of receptor is a muscarinic receptor?
Which type of receptor is a muscarinic receptor?
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What is the primary effector organ for M2 receptors?
What is the primary effector organ for M2 receptors?
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Which agent can block muscarinic receptors?
Which agent can block muscarinic receptors?
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What type of nicotinic receptor is found at the autonomic ganglia?
What type of nicotinic receptor is found at the autonomic ganglia?
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In which area are M5 receptors currently being investigated?
In which area are M5 receptors currently being investigated?
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Which type of fibers release acetylcholine?
Which type of fibers release acetylcholine?
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What is the primary enzyme involved in the synthesis of acetylcholine?
What is the primary enzyme involved in the synthesis of acetylcholine?
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What initiates the release of acetylcholine at the axon terminal?
What initiates the release of acetylcholine at the axon terminal?
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What process is responsible for the termination of acetylcholine activity in the synaptic cleft?
What process is responsible for the termination of acetylcholine activity in the synaptic cleft?
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Which ions are involved in the depolarization of the postsynaptic membrane when acetylcholine binds to its receptors?
Which ions are involved in the depolarization of the postsynaptic membrane when acetylcholine binds to its receptors?
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What is the role of cyclic AMP in cholinergic transmission?
What is the role of cyclic AMP in cholinergic transmission?
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Where is acetylcholine stored prior to release?
Where is acetylcholine stored prior to release?
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What occurs to acetylcholine after it binds to receptors on the postsynaptic membrane?
What occurs to acetylcholine after it binds to receptors on the postsynaptic membrane?
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What is the effect of cholinesterases on acetylcholine?
What is the effect of cholinesterases on acetylcholine?
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Which of the following describes the onset and duration of muscarinic action compared to nicotinic action?
Which of the following describes the onset and duration of muscarinic action compared to nicotinic action?
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What is the primary clinical use of anticholinesterases such as neostigmine?
What is the primary clinical use of anticholinesterases such as neostigmine?
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Which of the following statements about muscarinic and nicotinic actions is correct?
Which of the following statements about muscarinic and nicotinic actions is correct?
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What is the role of acetate in cholinergic transmission?
What is the role of acetate in cholinergic transmission?
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Which receptor subtype is primarily associated with smooth muscles and secretory glands?
Which receptor subtype is primarily associated with smooth muscles and secretory glands?
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What type of receptors are nicotinic receptors classified as?
What type of receptors are nicotinic receptors classified as?
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Which substance can block nicotinic receptors at high doses?
Which substance can block nicotinic receptors at high doses?
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Which subtype of muscarinic receptors is primarily located in the heart?
Which subtype of muscarinic receptors is primarily located in the heart?
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What effect does atropine have on muscarinic receptors?
What effect does atropine have on muscarinic receptors?
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What is primarily responsible for transmitting impulses away from the synapse?
What is primarily responsible for transmitting impulses away from the synapse?
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Which type of synapse allows for faster transmission of signals?
Which type of synapse allows for faster transmission of signals?
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What distinguishes chemical synapses in terms of fatigue compared to electrical synapses?
What distinguishes chemical synapses in terms of fatigue compared to electrical synapses?
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Which statement about conduction direction in electrical synapses is true?
Which statement about conduction direction in electrical synapses is true?
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What factor characterizes the synaptic cleft in cholinergic transmission?
What factor characterizes the synaptic cleft in cholinergic transmission?
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Which type of synapse is more commonly found in the nervous system?
Which type of synapse is more commonly found in the nervous system?
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What is the role of neurotransmitters in chemical synapses?
What is the role of neurotransmitters in chemical synapses?
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How does the speed of conduction compare between electrical and chemical synapses?
How does the speed of conduction compare between electrical and chemical synapses?
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Which factors are involved in the synthesis of acetylcholine?
Which factors are involved in the synthesis of acetylcholine?
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What occurs during the release of acetylcholine at the axon terminal?
What occurs during the release of acetylcholine at the axon terminal?
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Which process is responsible for the inhibition of neurotransmission in cholinergic transmission?
Which process is responsible for the inhibition of neurotransmission in cholinergic transmission?
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Where are acetylcholine molecules primarily stored before release?
Where are acetylcholine molecules primarily stored before release?
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What is the primary effect of acetylcholine binding to its receptors on the postsynaptic membrane?
What is the primary effect of acetylcholine binding to its receptors on the postsynaptic membrane?
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Which statement accurately describes the role of calcium ions in cholinergic transmission?
Which statement accurately describes the role of calcium ions in cholinergic transmission?
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What is one of the mechanisms that leads to hyperpolarization following acetylcholine receptor activation?
What is one of the mechanisms that leads to hyperpolarization following acetylcholine receptor activation?
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How does acetylcholine concentration decrease in the synaptic cleft after its release?
How does acetylcholine concentration decrease in the synaptic cleft after its release?
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Study Notes
Cholinergic Transmission
- A functional connection between a neuron and a second cell such as neuron, muscle, or gland
Synapse
-
Electrical Synapse
- Gap junctions between pre and postsynaptic membranes
- Allows direct transmission of electrical depolarization waves
- Rare
- Resistant to fatigue
- Conduction in both directions
- Faster speed
-
Chemical Synapse
- Junction between pre and postsynaptic membranes mediated by chemicals
- Very common
- Chemical substances are released at nerve endings for transmission of nerve impulses
- Shows fatigue
- Conduction occurs in one direction
- Slower speed
Types of Transmission
-
Cholinergic Transmission:
- Mediated by Acetylcholine
-
Adrenergic Transmission:
- Mediated by Noradrenaline
Sites of Acetylcholine Release
- All pre-ganglionic fibers
- Sympathetic pre-ganglionic fibers to adrenal medulla
- All parasympathetic post-ganglionic fibers
- Sympathetic post-ganglionic fibers to sweat glands and skeletal muscle blood vessels
- Motor end plate (Neuromuscular junction)
- Some synapses in the CNS
Synthesis of Acetylcholine
- Acetyl coenzyme A + choline → acetylcholine + coenzyme A in presence of choline acetyltransferase (CAT)
- ATP and glucose are required to form acetyl coenzyme A
Storage of Acetylcholine
- Stored in nerve terminals inside minute vesicles
- Each vesicle contains thousands of acetylcholine molecules
- Some acetylcholine molecules are found free in the cytoplasm
Release of Acetylcholine
- Action potential reaches axon terminal
- Depolarization occurs
- Increased permeability to calcium ions
- Calcium ions influx
- Calcium binds to the vesicles and moves them to the membrane
- Vesicles rupture, releasing acetylcholine into the synaptic cleft through exocytosis
- Acetylcholine then binds to its receptors on the postsynaptic membrane
Mechanisms of Action
- Acetylcholine binds to receptors on the postsynaptic membrane
-
Ligand-gated Ion Channels:
- Sodium and calcium influx leads to depolarization (stimulation)
- Potassium efflux and chloride influx leads to hyperpolarization (inhibition)
-
G-protein Coupled Receptors
- Acetylcholine activates membrane enzymes such as adenyl cyclase
- Formation of second messenger called cyclic AMP from ATP
- Intracellular signaling
Removal of Acetylcholine
-
Diffusion:
- Diffusion to the surrounding area
- Decreases acetylcholine concentration
-
Hydrolysis:
- Choline esterase enzyme breaks down acetylcholine into acetic acid and choline
- Choline has a similar but weaker action as acetylcholine
- Choline is reuptaken into the nerve ending and recycled to form new acetylcholine
- Acetate diffuses into the blood
-
Reuptake:
- Not yet completely defined
Anticholinesterases
- Neostigmine blocks the action of cholinesterase
- Prolongs the action of acetylcholine
- Used to treat certain diseases such as myasthenia gravis
Action of Acetylcholine
- Muscarinic Action: - Similar to the action of muscarine - Muscarine is an alkaloid from poisonous mushrooms - Affects smooth muscles and glands supplied by parasympathetic and sympathetic cholinergic nerve fibers - Slow onset - Prolonged duration - Antagonist is atropine
-
Nicotinic Action:
- Similar to the action of nicotine
- Nicotine is derived from tobacco
- Affects autonomic ganglia, neuromuscular junction, and adrenal medulla (secretion of adrenaline and noradrenaline)
- Rapid onset
- Short duration
- Antagonists: ganglion and neuromuscular blockers
Acetylcholine Receptors (Cholinergic Receptors)
-
Muscarinic Receptors:
- Ligand-gated ion channels
- Located at effector organs of all postganglionic cholinergic nerve terminals
- Subtypes:
- M1: Brain and autonomic ganglia
- M2: Heart
- M3: Smooth muscles and secretory glands
- M4: Pancreas
- M5: Under investigation
- Stimulated by muscarine
- Blocked by atropine
-
Nicotinic Receptors:
- G-protein coupled receptors
- Located at autonomic ganglia, adrenal medulla, motor endplates
- Subtypes:
- Neural nicotinic (Nn): Autonomic ganglia and adrenal medulla
- Muscle nicotinic (Nm): Motor endplate
- Stimulated by nicotine (small dose)
- Blocked by nicotine (large dose)
Cholinergic Transmission
- Definition: A functional connection between a neuron and another cell, including neurons, muscle, or glands.
-
Synapse Structure:
- Pre-synaptic Neuron: Transmits impulses towards the synapse.
- Synaptic Cleft: A 10-30 nm space filled with interstitial fluid that separates the nerve ending from the next neuron or effector organ.
- Post-synaptic Neuron: Transmits impulses away from the synapse.
Types of Synapses
-
Electrical Synapse:
- A gap junction connects the pre and postsynaptic membranes.
- Rare occurrence.
- Allows direct transmission of electrical depolarization waves from the presynaptic to the postsynaptic neuron.
-
Chemical Synapse:
- A junction mediated by chemicals between the pre and postsynaptic membranes.
- Very common.
- Chemicals are released at nerve endings, transmitting nerve impulses from one neuron to another.
Electrical Synapse vs. Chemical Synapse
- Presence: Rare vs. Very common.
- Mechanism: Direct transmission vs. Chemically mediated.
- Fatigue: Resist fatigue vs. Show fatigue.
- Conduction: Both directions vs. One direction.
- Speed: Faster vs. Slower.
Types of Synaptic Transmission
- Cholinergic Transmission: Involving acetylcholine as the neurotransmitter.
- Adrenergic Transmission: Involving noradrenaline as the neurotransmitter.
Acetylcholine Release Sites
- All pre-ganglionic fibers.
- Sympathetic pre-ganglionic fibers to the adrenal medulla.
- All parasympathetic post-ganglionic fibers.
- Sympathetic post-ganglionic fibers to sweat glands and skeletal muscle blood vessels.
- Motor end plate (neuro-muscular junction).
- Some synapses in the central nervous system (CNS).
Acetylcholine Synthesis
- Acetyl co-A reacts with choline in the presence of choline acetyltransferase (CAT) enzyme.
- Acetyl co-A + Choline → Acetylcholine + co-A.
- ATP and glucose are required to form acetyl co-A.
Acetylcholine Storage
- Stored in nerve terminals within minute vesicles.
- Each vesicle contains more than one thousand acetylcholine (Ach) molecules (5000-10,000).
- Some molecules are found free in the cytoplasm.
Acetylcholine Release
- When an action potential reaches the axon terminal:
- Depolarization occurs.
- Permeability to Ca ions increases.
- Ca influx occurs.
- Calcium binds to the vesicles and moves them toward the membrane.
- Vesicles rupture and release acetylcholine into the synaptic cleft via exocytosis.
- Acetylcholine passes through the cleft and binds to its receptors on the postsynaptic membrane.
Acetylcholine Mechanism of Action
- Acetylcholine binds to receptors on the postsynaptic membrane.
-
Ligand-gated ion channels:
- Sodium (Na) and calcium (Ca) influx leads to depolarization (stimulation).
- Potassium (K) efflux and chloride (Cl) influx leads to hyperpolarization (inhibition).
-
G-protein coupled receptors:
- Activates membrane enzymes, such as adenyl cyclase.
- Formation of the second messenger, cyclic AMP (cAMP), from ATP.
- cAMP triggers intracellular signal transduction pathways.
Acetylcholine Removal
- Diffusion: Acetylcholine diffuses into the surrounding area, decreasing its concentration.
-
Hydrolysis:
- Acetylcholinesterase enzyme breaks down acetylcholine into acetic acid and choline.
- Choline has an action similar to acetylcholine, but weaker. Choline is reuptaken back into the nerve ending to be recycled to form new acetylcholine.
- Acetate ions diffuse into the blood.
- Reuptake: The mechanism is not fully understood.
Clinical Considerations
- Cholinesterases: Keep the action of acetylcholine localized to the site of liberation.
-
Anticholinesterases:
- Block the action of cholinesterase.
- Prolong the action of acetylcholine.
- Used to treat diseases like myasthenia gravis.
Actions of Acetylcholine
-
Muscarinic Action:
- Similar to the action of muscarine, an alkaloid derived from poisonous mushrooms.
- Affects smooth muscles and glands supplied by parasympathetic and sympathetic cholinergic nerve fibers.
-
Nicotinic Action:
- Similar to the action of nicotine, derived from tobacco.
- Affects autonomic ganglia, the neuromuscular junction, and the adrenal medulla (secretion of adrenaline and noradrenaline).
Muscarinic Action vs. Nicotinic Action
- Onset: Slow vs. Rapid.
- Duration: Prolonged vs. Short.
- Antagonist: Atropine vs. Ganglion and neuromuscular blockers.
Acetylcholine Receptors (Cholinergic Receptors)
-
Muscarinic Receptors:
- Ligand-gated ion channels.
- Found at effector organs for all post-ganglionic cholinergic nerve terminals.
-
Nicotinic Receptors:
- G-protein coupled receptors.
- Found at autonomic ganglia, the adrenal medulla, and the motor end plate.
Muscarinic Receptor Subtypes
- M1: Brain and autonomic ganglia.
- M2: Heart.
- M3: Smooth muscles and secretory glands.
- M4: Pancreas.
- M5: Under investigation.
Nicotinic Receptor Subtypes
-
Neural nicotinic (Nn):
- Autonomic ganglia
- Adrenal medulla.
-
Muscle nicotinic (Nm):
- Motor end plate.
Acetylcholine Receptor Stimulation and Blockade
- Muscarinic Receptor Stimulation: Muscarine.
- Muscarinic Receptor Blockade: Atropine.
- Nicotinic Receptor Stimulation: Nicotine (small dose).
- Nicotinic Receptor Blockade: Nicotine (large dose).
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