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Questions and Answers
What type of receptor is primarily associated with the contraction response to norepinephrine in smooth muscle cells?
What type of receptor is primarily associated with the contraction response to norepinephrine in smooth muscle cells?
Which neurotransmitter is released during sympathetic stimulation leading to relaxation of smooth muscle cells?
Which neurotransmitter is released during sympathetic stimulation leading to relaxation of smooth muscle cells?
How do varicosities function in the neuromuscular system?
How do varicosities function in the neuromuscular system?
What is the mechanism of action for muscarinic receptors in muscle contraction?
What is the mechanism of action for muscarinic receptors in muscle contraction?
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What is the primary structure associated with the synaptic cleft in smooth muscle cells?
What is the primary structure associated with the synaptic cleft in smooth muscle cells?
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What triggers the release of Ca+ from the sarcoplasmic reticulum in muscle cells?
What triggers the release of Ca+ from the sarcoplasmic reticulum in muscle cells?
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What occurs during the muscle action potential as Na+ and K+ channels fluctuate?
What occurs during the muscle action potential as Na+ and K+ channels fluctuate?
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Which of the following describes the structure of a synaptic cleft?
Which of the following describes the structure of a synaptic cleft?
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Which mechanism describes the coupling of the action potential to neurotransmitter release?
Which mechanism describes the coupling of the action potential to neurotransmitter release?
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What condition can affect the function at the neuromuscular junction?
What condition can affect the function at the neuromuscular junction?
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What is the primary role of the sarcoplasmic reticulum in muscle cells?
What is the primary role of the sarcoplasmic reticulum in muscle cells?
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Which statement is true regarding ion channels in muscle cells?
Which statement is true regarding ion channels in muscle cells?
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What is the main function of acetylcholine at the neuromuscular junction?
What is the main function of acetylcholine at the neuromuscular junction?
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Which channel is primarily responsible for the influx of calcium ions during muscle action potential?
Which channel is primarily responsible for the influx of calcium ions during muscle action potential?
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What is a primary characteristic of myasthenia gravis?
What is a primary characteristic of myasthenia gravis?
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How does acetylcholinesterase contribute to muscle action?
How does acetylcholinesterase contribute to muscle action?
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Which of the following describes a characteristic of the synaptic cleft?
Which of the following describes a characteristic of the synaptic cleft?
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In the context of muscle contraction, what happens when calcium binds to troponin?
In the context of muscle contraction, what happens when calcium binds to troponin?
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Which receptors are primarily affected in Lambert-Eaton myasthenic syndrome?
Which receptors are primarily affected in Lambert-Eaton myasthenic syndrome?
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In which of the following scenarios would you expect impaired muscle contraction?
In which of the following scenarios would you expect impaired muscle contraction?
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What is primarily responsible for the recycling of acetylcholine at the neuromuscular junction after its release?
What is primarily responsible for the recycling of acetylcholine at the neuromuscular junction after its release?
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Which muscle cell signaling process is involved in the action potential that leads to contraction?
Which muscle cell signaling process is involved in the action potential that leads to contraction?
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Study Notes
Anatomy of a Muscle Cell
- The membrane of a muscle cell is called the sarcolemma
- The cytoplasm of a muscle cell is called the sarcoplasm
- The sarcoplasmic reticulum is a specialized form of smooth endoplasmic reticulum
- The sarcoplasmic reticulum contains calcium ion pumps and no ribosomes
- T tubules are invaginations of the sarcolemma that carry action potentials deep into the muscle cell
- T tubules are connected to the sarcoplasmic reticulum by protein complexes.
Ion Channels
- Ion channels are very fast
- Ion channels are passive and cannot be coupled to an energy source
- Ion channels are selective for certain ions
- Ion channels can fluctuate between open and closed states
- Different ion channels are gated by different mechanisms.
Action Potential
- The action potential is an all or none event
- The action potential is always around 100mV
- The action potential lasts for a few milliseconds
- Sodium ions flow into the cell during the action potential
- Potassium ions flow out of the cell during the action potential.
Synapses
- Electrical synapses are formed by gap junctions between two neurons.
- Electrical synapses allow for direct flow of electrical currents.
- Chemical synapses transmit signals through neurotransmitters.
Chemical Synapse - Function
- Neurotransmitters are stored in vesicles
- Action potentials arriving at the synapse cause voltage-gated calcium channels to open.
- Calcium ions bind to synaptotagmin which initiates the fusion of the vesicle membrane with the plasma membrane.
Vesicle-Membrane Fusion
- SNARE proteins facilitate vesicle-membrane fusion.
- SNARE proteins are anchored membrane proteins.
Recycling of the Membrane at the Synapse
- Membranes can fuse by a "kiss-and-run" mechanism
- Membranes can be recycled through clathrin-mediated endocytosis.
- Docked vesicles can be exchanged and are quality controlled.
- Recycling via invagination is much slower.
Synaptic Cleft
- The synaptic cleft is typically 20nm wide
- The synaptic cleft is shielded from the extracellular space by the basal lamina.
- Dense filaments can traverse the synaptic cleft
- Neurotransmitters are released into the synaptic cleft
- The synaptic cleft has a specialized adhesive junction.
Neuromuscular Junction
- One nerve fiber innervates each motor endplate.
- When an impulse arrives at the neuromuscular junction, it triggers calcium influx
- Acetylcholine is the neurotransmitter at the neuromuscular junction.
- Acetylcholine binds to nicotinic cholinergic receptors, which are concentrated on the motor endplate.
- Binding of acetylcholine generates an endplate potential, which leads to a muscle action potential
- This increases calcium concentration in the muscle.
Acetylcholine Receptor
- Acetylcholine receptors are classified based on their pharmacological profile:
- Nicotinic Acetylcholine Receptor (nAChR)
- Muscarinic Acetylcholine Receptor (mAChR)
- The nicotinic acetylcholine receptor is composed of five subunits and is a transmitter-gated sodium channel.
Motor Endplate
- The motor endplate consists of junctional folds, which are thickened muscle membranes
- The synaptic cleft of the neuromuscular junction is similar in structure to the synaptic clefts found in other synapses
- Acetylcholine receptors are concentrated on the tops of the folds
- Acetylcholinesterase breaks down acetylcholine into acetate and choline which is transported back into the presynaptic terminal.
Muscle Action Potential
- Binding of acetylcholine to the nicotinic acetylcholine receptor opens sodium channels, leading to an influx of sodium ions.
- Opening of voltage-gated calcium channels on the sarcolemma allows calcium ions to flow into the cell.
- Voltage-gated calcium channels on the sarcoplasmic reticulum release stored calcium ions into the cytoplasm.
Motor Action Potential
- Ryanodine receptors, activated by voltage-sensitive DHP receptors, cause the release of calcium from the sarcoplasmic reticulum
- Calcium ions bind to troponin, which triggers myosin contraction
- Calcium can act as a second messenger for cellular functions.
Pathophysiological Conditions Associated with the Neuromuscular Junction
- Autoimmune disorders can affect the neuromuscular junction
- These disorders can cause antibodies against:
- AChR and MuSK in myasthenia gravis
- VGCC in Lambert–Eaton myasthenic syndrome
- VGKC in neuromyotonia (Isaacs’ syndrome)
Myasthenia Gravis
- Myasthenia gravis is characterized by myasthenic fatigue.
- Myasthenia gravis is an autoimmune disorder most commonly caused by anti-AChR antibodies.
- These antibodies cause:
- Induced receptor endocytosis
- Damage to the membrane by activation of the compliment system
- Blockage of the receptor's active site.
- The thymus is often hyperplastic with active germinal centers in patients with Myasthenia gravis.
Myasthenia Gravis - Clinical Features
- Muscle weakness and fatigue are the hallmark symptoms of Myasthenia gravis.
- Severe cases, may experience crisis with systemic infections or disorders.
- The symptoms of Myasthenia gravis can wax and wane, experiencing periods of exacerbation and remission.
- Cranial muscles are often affected first.
- Muscle weakness may develop within 3 years or never develop at all.
- Deep tendon reflexes remain intact.
Nerve Endings in Smooth and Cardiac Muscle
- THERE ARE NO NEUROMUSCULAR JUNCTIONS in smooth or cardiac muscle
- There are no recognizable endplates or other postsynaptic specializations.
- Smooth and cardiac muscle cells are innervated by nerves that run along the muscle cells and groove them
- Branches of these neurons have enlargements called varicosities, which contain synaptic vesicles
- Each neuron can have up to 20,000 varicosities.
- Transmitters are likely released at each varicosity
- One single neuron can innervate many effector cells.
Adrenergic Receptors
- Adrenergic receptors are found on smooth and cardiac muscle cells (in T-tubules).
- Adrenergic receptors bind to norepinephrine and epinephrine
- Adrenergic receptors are G-protein coupled receptors.
Neurotransmitter Signaling in Smooth Muscle Cells
- Smooth muscle cell activity is modulated by neurotransmitters:
- Norepinephrine and epinephrine from sympathetic stimulation:
- Contraction (predominant) via alpha-1-AR receptor
- Relaxation (predominant) via beta-2-AR receptor
- Acetylcholine from parasympathetic stimulation:
- Contraction (direct) via muscarinic receptor on the smooth muscle cell
- Relaxation (indirect) via muscarinic receptor on the endothelial cell
- Angiotensin II: Contraction via AT-II receptor
- Vasopressin: Contraction via vasopressin receptor
- Endothelin: Contraction via endothelin receptor
- Adenosine: Relaxation via adenosine receptor
- Norepinephrine and epinephrine from sympathetic stimulation:
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Description
This quiz explores the anatomy of muscle cells, including the roles of the sarcolemma, sarcoplasm, and sarcoplasmic reticulum. It also delves into the mechanisms of ion channels and the properties of action potentials. Test your understanding of these critical physiological concepts.
