6. Excitable Cells: Neural Communication Flashcards
(270 cards)
1
Q
What are the two main nervous systems?
A
- Central nervous system
- Peripheral nervous system
2
Q
What structures make up the CNS?
A
- Brain
- Spinal cord
3
Q
What structures make up the PNS?
A
All neuronal elements outside the brain and sponal cord:
- Cranial and spinal nerves -> Made of sensory and motor nerves
- Associated ganglia
- Supporting cells (e.g. Schwann cells)
4
Q
Are sensory peripheral nerves divided into autonomic/somatic, parasympathetic/sympathetic, etc.?
A
They are sometimes divided into somatic and visceral afferent fibres, but CHECK THIS.
5
Q
Draw a diagram to show the divisions of the nervous system.
A
6
Q
What is the embryological origin of the central and peripheral nervous systems?
A
- CNS -> Neural tube
- PNS -> Neural crest
7
Q
Describe the process by which peripheral nervous system cells develop (in terms of embryology).
A
They undergo:
- Specification
- Migration
- Differentiation
- Functional specification
8
Q
What are the two divisions of the sensory division of the nervous system?
A
- Somatic sensory
- Consciously perceived
- Touch, pain, hearing, etc.
- Visceral sensory
- Not consciously perceived
- Stretch, chemical changes, taste, etc.
9
Q
What are the two types of peripheral neurons?
A
10
Q
Draw the structure of a reflex arc.
A
11
Q
What are ganglia?
A
Egg-shaped structures containing cell bodies of neurons and glial cells supported by connective tissue.
i.e. It is where the cell bodies of neurons are.
12
Q
What are unipolar, bipolar and multipolar neurons? Where is each found?
A
This essentially refers to the number of processes (e.g. axons) that come out of the cell body:
- Unipolar -> Sensory neurons with cell bodies in spinal and cranial nerve ganglia.
- Bipolar neurons -> Relatively rare. They are sensory neurons found in olfactory epithelium, the retina of the eye, and ganglia of the vestibulocochlear nerve.
- Multipolar neurons -> Most common. They are located in the central nervous system (brain and spinal cord) and in autonomic ganglia.
13
Q
Where do sensory neurons have ganglia?
A
Near the spinal cord -> These are called DORSAL ROOT GANGLIA
14
Q
What is found in dorsal root ganglia?
A
The cell bodies of sensory neurons.
15
Q
Where do sensory neurons usually terminate?
A
At interneurons of the CNS.
16
Q
What are some different categories of sensory neuron receptors?
A
- Thermoreceptors – Respond to changes in temperature
- Photoreceptors – React to light
- Chemoreceptors – Respond to chemicals
- Mechanoceptors – Respond to pressure, touch vibrations
- Nociceptors – Respond to pain
17
Q
Where are sensory receptors found?
A
They are found at the ends of sensory neurons.
18
Q
Give some examples of sensory nerve endings and what they detect. [IMPORTANT]
A
- Meissner corpuscle -> Fine touch
- Merkel disc -> Touch
- Pacinian corpuscle -> Coarse touch, Pressure, Vibration
- Free nerve endings -> Heat, Pain
- Ruffini endings -> Stretch
Remember:
- Meissner sounds smooth so it detects smooth touch, while Merkel sounds rough so it detects coarser touch
- ViP STaR = Vibration is detected by Pacinian corpuscles, while Stretch and Temperature are detected by Ruffini endings
- Free nerve endings detect heat and pain
19
Q
What stimulus do Meissner corpuscles detect?
A
Fine touch
20
Q
What stimulus do Pacinian corpuscles detect?
A
Coarse touch, Vibration, Pressure
21
Q
What stimulus do free nerve endings detect?
A
Pain, Heat, Touch
22
Q
What stimulus do Ruffini’s corpuscles detect?
A
Stretch
23
Q
What stimulus do Merkel’s disks detect?
A
Touch
24
Q
Draw the positions and appearance of different sensory nerve endings near the skin.
A
Remember: The two M’s are in the epidermis along with the free nerve endings, while the rest are in the dermis.
25
What is this?
Pacinian corpuscle
26
What is this?
Meissner's corpuscle
27
Compare the motor neurons of somatic and autonomic nervous systems.
Somatic motor neurons:
* Single neuron network
* Monosynaptic
Autonomic motor neurons:
* Two neuron network
* Disynaptic
28
Compare the neurotransmitters that the somatic, parasympathetic and sympathetic nervous systems use.
* Somatic -\> Acetylcholine
* Parasympathetic -\> Acetylcholine (at both synapses)
* Sympathetic -\> Acetylcholine (at ganglion) + Noradrenaline (at effector)
29
Name the different types of ganglia that the spec mentions. What is found in each?
* Dorsal root ganglia (where sensory neuron cell bodies are)
* Sympathetic (where postganglionic neuron cell bodies are)
* Parasympathetic (where postganglionic neuron cell bodies are)
* Enteric (where postganglionic neuron cell bodies are)
30
What parts of the body do the sympathetic, parasympathetic and enteric nervous systems provide motor supply to?
Sympathetic:
* Muscles
* Viscera
* Cardiac and smooth muscle
Parasympathetic:
* Viscera
* Cardiac and smooth muscle
* No musculo-skeletal supply
Enteric:
* Intrinsic nervous system of gut
31
What is the pre-ganglionic neurotransmitter?
Acetylcholine
32
Compare the general positions of ganglia in the somatic, parasympathetic and sympathetic nervous systems.
* Somatic -\> No ganglia
* Parasympathetic -\> Usually within (or near to) effector organs
* Sympathetic -\> Usually within discrete ganglia closer to the spinal cord (e.g. paravertebral ganglia)
33
At what spinal levels do sympathetic and parasympathetic nerves arise from?
* Parasympathetic -\> Craniosacral
* Sympathetic -\> Tharcolumbar
Remember: PSP
34
Describe the different sympathetic ganglia. [IMPORTANT]
Paravertebral ganglia:
* Two **paravertebral ganglia** run either side of the spinal cord -\> Supply multiple organs
* At the top of these are **cervical ganglia** -\> Supply the head and thorax (heart and lungs)
Prevertebral (i.e. between the paravertebral ganglia and the target organs):
* **Coeliac ganglia** -\> Supply foregut
* **Superior mesenteric ganglia** -\> Supply midgut
* **Inferior mesenteric ganglia** -\> Supply pelvic organs
35
What are the pre-ganglionic nerves that supply the coeliac, superior mesenteric and inferior mesenteric ganglia (sympathetic)? What body parts do these supply?
* Coeliac ganglion -\> Greater splanchnic nerve
* Supplies the foregut
* Superior mesenteric -\> Lesser splanchnic nerve
* Supplies the midgut
* Inferior mesenteric -\> Least splanchnic nerves
* Supplies the pelvic organs
36
What are the different cervical ganglia and what do they supply? Is this sympathetic or parasympathetic?
* Superior cervical ganglion -\> Head
* Middle cervical and stellate ganglia -\> Heart and lungs
This is sympathetic.
37
What do the sympathetic paravertebral chains allow?
They allow nerve fibres to travel to spinal nerves that are superior and inferior to the one in which they originated.
38
Where do the cervical ganglia receive nerve fibres from?
They receive fibres from the paravertebral chain, since no nerve roots come from the cervical region.
39
What exact fibres modulate the enteric nervous system?
* Pre-ganglionic parasympathetic fibres
* Vagus nerve
* Sacral fibres
* Post-ganglionic sympathetic fibres
* From prevertebral ganglia
40
What do sacral parasympathetic fibres supply?
Meissner’s and Auerbach’s plexus (enteric nervous system), as well as the lower gut and urogenital tract.
41
Draw the structure of the enteric nervous system.
42
What is the role of the enteric nervous system?
Coordinates the activities of the gut
43
What are the three types of neuron in the plexuses of the gut wall?
* Sensory
* Motor
* Secretomotor -\> Induce a gland to secrete a substance
44
Describe the formation of the autonomic nervous system.
* The peripheral nervous system is derived from the neural crest, which forms when the neural tube closes.
* These then undergo migration and the time of migration determines the fate of the cells:
* First cells -\> Form the enteric nervous system.
* Next -\> Crest cells migrate through the somites to form the segmental paravertebral ganglia (sympathetic)
* Finally -\> Parasympathetic ganglia and prevertebral sympathetic ganglia form.
* Pre-ganglionic fibres of the autonomic nervous system are CNS neurons that lie in the intermediate part of the spinal cord and are patterned by Shh signals from the notochord.
45
Why are the paravertebral chain ganglia arranged segmentally?
* The neural crest migrates through the cranial half of each somite and forms the segmental sympathetic chain ganglia.
* The caudal half of each somite contains inhibitory molecules that prevent neural crest migration.
46
How is the enteric nervous system formed?
Neural crest cells arise from the cervical levels, invade the gut and then colonise the entire gut in a caudal direction.
47
What is Hirschprung's disease, what causes it and what are the symptoms?
* Caused by failure of neural crest cells to invade (or survive in) the gut wall
* This means that the enteric nervous system doesn't develop fully
* The symptoms include constipation and megacolon (swelling of the colon and lack of peristaltic movement)
48
What are the three points where pre-ganglionic nerve fibres terminate in the sympathetic nervous system?
1. Some terminate in the ganglia
2. Some reach the paravertebral ganglia, go up or down the chain, and then terminate at a different spinal level
3. Some pass to pre-vertebral/midline ganglia via the splanchnic nerves (without synapsing at the paravertebral chain)
49
What are midline ganglia?
They are pre-vertebral ganglia (sympathetic). [CHECK THIS - DOES IT ACTUALLY MEAN PARAVERTEBRAL?]
50
What does the sympathetic and parasympathetic supply to the head come from?
* Sympathetic -\> From the superior cervical ganglion (at the top of the paravertebral chain)
* Parasympathetic -\> Cranial nerves
51
Are cranial nevres parasympathetic or sympathetic?
Parasympathetic
52
What are the four cranial nerves you need to know about and what number are they?
* III - Occulomotor
* XII - Facial
* IX - Glossopharyngeal
* X - Vagus
53
Which cranial nerve is the occulomotor nerve and what does it supply?
* III
* Supplies the iris of the eye (via the ciliary ganglion)
54
Which cranial nerve is the facial nerve and what does it supply?
* VII
* Supply lacrimal glands and nasal mucosa (via the pterygopalatine ganglion)
* Supply salivary glands (via submandibular ganglion )
55
Which cranial nerve is the glossopharyngeal nerve and what does it supply?
* IX
* Supplies parotid salivary gland (via the otic ganglion)
56
Which cranial nerve is the vagus nerve and what does it supply?
* X
* Supplies the organs of the thorax and abdomen
57
Describe how peristalsis happens.
* Food in gut causes mechanical release of serotonin
* This stimulates cells in the submucosal plexus which in turn stimulate the myenteric plexus
* This causes peristalsis to happen
58
Compare the structures at the effector-end of somatic and autonomic motor neurons.
* Somatic motor neurons end in a synapse (motor end-plate)
* Autonomic nerves end in varicosities, which are a series of enlargements where neurotransmitter is released onto the effector
59
What is the exception to the rule that sympathetic post-ganglionic nerves use noradrenaline?
Sweat glands receive cholinergic control.
60
Describe how the adrenal gland relates to the sympathetic nervous system.
It is stimulated by pre-ganglionic fibres (by ACh release) to release catecholamines into the blood.
61
Which nerve innverates the adrenal gland?
Greater splanchnic
62
How are cardiovascular effects of the sympathetic system coordinated?
By CNS control centres.
63
What is Horner's syndrome and what are the symptoms?
* Caused by lesions of the superior cervical ganglion (that supplies the head)
* Symptoms:
* Permanent constriction of the pupil
* Drooping eyelid (ptosis)
* A dry face and flushed face
64
How can excessive sweating (hyperhidrosis) be treated?
* Sympathetic chain can be cut to prevent sympathetic stimulation
OR
* Region injected with Botulinum toxin.
65
Is crying a sympathetic or parasympathetic action?
Parasympathetic
66
For the heart, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Increased heart rate -\> Beta 1 (and beta 2)
* Increased force of contraction -\> Beta 1 (and beta 2)
* Increased conduction velocity
Parasympathetic:
* Decreased heart rate
* Decreased force of contraction
* Decreased conduction velocity
67
For arteries, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Constriction mostly (alpha 1)
* Dilation of some (beta 2)
Parasympathetic:
* Dilation
68
For veins, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Constriction mostly (alpha 1)
* Dilation of some (beta 2)
Parasympathetic: None
69
For lungs, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Bronchial muscle relaxation (beta 2)
Parasympathetic:
* Bronchial muscle constriction
* Increased bronchial gland secretions
70
For the GI tract, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Decreased motility (beta 2)
* Constriction of sphincters (alpha)
Parasympathetic:
* Increased motility
71
For the liver, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Glycogenolysis (beta 2 and alpha)
* Gluconeogenesis (beta 2 and alpha)
* Lipolysis (beta 2 and alpha)
Parasympathetic:
* Glycogen synthesis
72
For the kidney, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Renin secretion (beta 2)
Parasympathetic: None
73
For the bladder, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Detrusor relaxation (beta 2)
* Contraction of sphincter (alpha)
Parasympathetic: None
74
For the uterus, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Contraction of pregnant uterus (alpha)
* Relaxation of pregnant and non-pregnant uterus (beta 2)
Parasympathetic: None
75
For the eye, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Dilates pupil (alpha)
Parasympathetic:
* Constricts pupil
* Increased lacrimal gland secretions
76
For the salivary glands, what is the effect of sympathetic and parasympathetic stimulation? What receptors does the sympathetic nervous system act on?
Sympathetic:
* Viscous salivary secretions (alpha)
Parasympathetic:
* Watery salivary secretions
77
What are the major parts of a neuron?
* Cell body
* Axon
* Dendrites
78
What is the difference between axons and dendrites?
* Axon
* Long process stretching from cell body
* Responsible for transmitting signals from cell body
* Dendrites
* Short cell processes
* Increase surface area for connecting with other axons and transmit signals to cell body
Remember: **_A_**xons **_A_**way
79
Describe the structural appearance of neuron cell bodies.
* Large nucleus
* Finely dispersed chromatin (indicative of a rich synthetic activity)
* Abundant rough endoplasmic reticulum (RER) with ribosomes
80
What are these purple structures?
Nissi bodies -\> They are the cell bodies of neurons after they have been stained purple with basic dye.
81
What are axons specialised for?
Transmission of information away from the cell body.
82
What is the diameter and length of axons?
* Microscopic in diameter (1μm – 1 mm)
* Some may extend a meter or even longer
83
What are dendritic spines?
Plastic structures in dendrites that are implicated in motivation, learning and memory.
84
Describe the two types of polarity of neurons.
* Structural
* One domain specialised to receive incoming signals and the other for sending signals
* Functional
* Unidirectional impulse propagation
85
What are the three types of cytoskeleton element in neurons and what does each do?
* Microtubulules -\> Transport
* Neurofilaments (a type of intermediate filament) -\> Maintain axonal structure
* Microfilaments -\> Allow changes in cell shape and act as scaffold for signal transduction systems
86
What molecules make up microfilaments in neurons?
Actin
87
What molecules make up microtubules in neurons?
Tubulin
88
What maintains neuronal polarity?
Bidirectional transport along the axon, using microtubules as skeletal tracks.
89
What are the two directions of transport in neurons?
* Anterograde -\> Towards the tip of axons
* Retrograde -\> Back from the tip of axons
90
What mechanochemical enzymes allow anterograde and retrograde transport along axons?
* Anterograde (towards the tip of axons) -\> Kinesin
* Retrograde (back from the tip of axons) -\> Dynein
91
What things are transported in a anterograde and retrograde direction along axons?
* Anterograde:
* Organelles
* Growth factors
* Neurotransmitters
* Retrograde:
* Endocytosis products to endosomes in cell body
92
What cells myelinate axons in the PNS and CNS?
* PNS -\> Schwann cells
* CNS -\> Oligodendrocytes
93
Describe how myelination of an axon by a Schwann cell occurs.
* Numerous layers of a Schawnn cell are wrapped around an axon
* Each turn forms a lamella of myelin
94
What is a mesaxon?
A pair of parallel plasma membranes of a Schwann cell, marking the point of edge-to-edge contact by the Schwann cell encircling the axon.
i.e. It is the point where the layers of a Schawann cell wrapped around an axon touch.
95
Do non-myelinated axons associate with Schwann cells?
Yes, they bury themselves in their cytoplasm (although the Schwann cells do not wrap around the axon like in myelinated axons).
96
What do oligodendrocytes do?
* Wrap myelin around several axons at once
* Found in the CNS
97
What are some functions of myelin?
* Provides support
* Facilitates fast axonal conduction
* Insulation
* Reduction of electrical capacitance for axons
98
What are the gaps between Schwann cells on an axon called?
Nodes of Ranvier
99
What is myelin made of?
* Phospholipids (70%)
* Proteins (30%)
100
What are 3 protein-encoding genes that are involved in myelin production?
* Protein zero (P0)
* Myelin basic protein (MBP)
* Proteolipid protein (PLP)
101
How do autoimmune diseases affect the nervous system and what are the symptoms?
* Caused by antibodies to glycosphingolipids
* Usually triggered by an acute infectious process
* Myelin regeneration occurs but there may also be axon damage
* Many patients become completely paralyzed and unable to breathe, 5% die from respiratory paralysis
An example is Guillain-Barre syndrome.
102
Do peripheral nerves contain just one axon?
No, they can contain very many.
103
How are neurons arranged in nerves?
Each nerve trunk contains:
* Bundles (fascicles) of fibres consisting of axons and Schwann cells
* Support cells and blood vessels
104
What are the 3 support tissues in nerves?
* Epineurium
* Perineurium
* Endoneurium
105
What do each of the epineurium, perineurium and endoneurium do?
* Epineurium
* Outer sheath binds individual nerve fascicles into a nerve trunk
* Perineurium
* Surrounds fasicles (bundles of axons)
* Endoneurium
* Surrounds axons and Schwann cells
106
What are the epineurium and endoneurium made of?
* Epineurium -\> Type I collagen and fibroblasts
* Endoneurium -\> Longitudinally orientated Type III collagen, fibroblasts and capillaries
107
What are the arrows pointing to?
Axons
108
In spinal nerves, are the dorsal and ventral roots sensory or motor?
* Dorsal is sensory (you can remember this because only sensory neurons synapse in the dorsal root ganglia)
* Ventral is motor
109
Draw the structural organisation of the PNS in a spinal nerve.
110
What different things do ganglia contain?
* Efferent and afferent axons
* Support cells (satellite cells)
* Blood vessels
* Support tissue -\> Perineural and epineural sheaths
111
Which cell body is found in autonomic ganglia?
The cell body of postganglionic autonomic nerves.
112
Describe the structure of dorsal root ganglia and autonomic ganglia.
113
Draw the structure of a synpase.
114
Can an axon innervate more than one muscle?
Yes
115
What is a motor unit?
A motor unit is made up of a motor neuron and the skeletal muscle fibers innervated by that motor neuron's axonal terminals.
116
What is the name for the connection between a somatic motor neuron and skeletal muscle?
Neuromuscular junction (NMJ)
117
What is the name for the synapse between an efferent neuron and its effector organ in the autonomic nervous system?
Neuroeffector junction
118
Draw the structure of a neuroeffector junction.
119
Compare the neurotransmitter release at the NMJ and neuroeffector junction.
It occurs from varicosities at the neuroeffector junction and this is much slower and more widespread.
120
What is myasthenia gravis and what are the symptoms it?
* Disease caused by antibodies blocking the AChR so signal is not transmitted
* Affects control of voluntary muscle:
* Drooping eyelids
* Impaired speech
* Breathing difficulties
* Blurred vision
* Muscle weakness in arms and legs
121
Describe the standard diagnostic test for myasthenia gravis. [EXTRA?]
122
Mutations in genes of proteins at NMJ can cause disease. How? How are these treated?
* Dominant mutations in NMJ genes cause disease
* Use gene silencing to silence mutated allele of these genes -\> Allow expression of normal wild type allele.
123
Can nerve axons regenerate?
* Peripheral nerve axons -\> Able to regenerate throughout life
* Central nervous system axons -\> Ability to regenerate decreases from birth
124
What cells direct nerve regeneration? How?
Schwann cells:
* When a nerve is damaged or injured the distal part atrophies – Wallerian degeneration
* Schwann cells divide and form hollow tube enclosed by endonerium
* Proximal end of the nerve fibre sends out sprouts towards those tubes
* Sprouts are attracted by growth factors produced by Schwann cells in the tubes Proceeds at 3-4 mm/day
125
What are the 3 types of nerve ending you need to know about?
* Sensory terminals
* Motor end-plates
* Sympathetic varicosities
126
Add flashcards on what terminal arbors are.
Are they just axon terminals?
127
Describe the segmental organisation of the somatic nervous system.
* There are 43 segments of nerves in the human body:
* 31 segments of nerves are in the spinal cord
* 12 segments in the brain stem
128
What are the the symptoms on loss of motor function?
Weakness and paralysis
129
What are the symptoms of irritation of sensory fibres?
Pain
130
What are the symptoms of damage to sensory fibres?
Loss of sensation
131
What is a mixed nerve?
* A mixed nerve is a nerve that contains both afferent and efferent nerves.
* MOST peripheral nerves are mixed nerves.
132
Where do visceral afferent fibres have their cell bodies?
In dorsal root ganglia.
133
What fibres do visceral afferent fibres often run alongside? What is the effect of this?
* Autonomic efferent nerves (since they both run to/from visceral organs)
* This can elicit involuntary autonomic reflexes (e.g. baroreceptor reflex) or may give sensation and mixed autonomic and voluntary somatic effects (e.g. micturition)
134
What spinal roots levels do sympathetic fibres arise from?
T1 - L2
135
What type of cell are adrenal medullary cells (that produce catecholamines)?
Modified sympathetic ganglion cells
136
Describe the myelination and speed of somatic and autonomic fibres.
Somatic:
* Mostly **myelinated** with **medium to fast** velocity
* Except **unmyelinated slow** C-type pain fibres
Autonomic:
* Pre-ganglionic -\> Mostly **myelinated** with **slow to medium** velocity
* Post-ganglionic -\> **Non-myelinated** with **slow** velocity
137
Nearly all cells have contractile elements. What are they and what are they used for?
* Actin and myosin
Used for:
* Movement
* Changing shape
* Intracellular movement of organelles
138
Nearly all cells have contractile elements (actin and myosin). What makes muscle cells different?
* Contractile machinery is permanently orientated
* Permits directional movements
139
What are the 3 types of muscle?
* Skeletal muscle
* Smooth muscle
* Cardiac muscle
140
What is striated muscle?
Muscle tissue that features repeating functional units called sarcomeres.
141
Compare skeletal, cardiac and smooth muscle in terms of whether they are striated or not.
* Skeletal -\> Striated
* Cardiac -\> Striated
* Smooth -\> Non-striated
142
Compare skeletal, cardiac and smooth muscle in terms of their nuclei.
* Skeletal -\> Multiple nuclei, peripherally located
* Cardiac -\> One nucleus, centrally located
* Smooth -\> One nucleus, centrally located
143
Draw a table to compare skeletal, cardiac and smooth muscle in terms of:
* Location
* Appearance
* Nuclei
* Innervation
144
In muscle cells, what are the names for these structures:
* Cell membrane
* Cytoplasm
* Smooth endoplasmic reticulum
* Mitochondria
* Contractile unit
* Cell membrane -\> Sarcolemma
* Cytoplasm -\> Sarcoplasm
* Smooth endoplasmic reticulum -\> Sarcoplasmic reticulum
* Mitochondria -\> Sarcosomes
* Contractile unit -\> Sarcomere
145
What is the name of the process by which muscle cells are generated?
Myogenesis
146
Which germ layer are muscle cells derived from?
Mesoderm
147
Which part of which germ layer do skeletal muscle cells develop from?
Somites (that form from parietal mesoderm, which is made when the lateral plate mesoderm splits into the parietal and splanchnic mesoderm)
148
Describe how skeletal muscle cells form from mesoderm.
* Somites are induced to differentiate into a sclerotome and dermomyotome -\> Due to sonic hedgehog (Shh) protein from notochord
* Progenitor cells of the dermomyotome then form Pax3+/Pax7+ expressing myoblasts that can divide and migrate
* Myoblasts exit the cell cycle & express transcription factors (MyoD and Myf5) that activate genes for muscle cells
* Myoblasts fuse to form multinucleate cells, called myotubes
* Myotubes develop into myocytes (fibres)
149
What are myoblasts?
* Embryonic precursors of myocytes (also called muscle cells).
* Myoblasts differentiate into muscle cells through a process called myogenesis.
150
What myoblast is a major muscle precursor cell and what cells does it produce?
Pax3+/Pax7+ myoblast
151
What are myotubes?
The multinucleate tubes formed by the fusion of multiple myoblasts. When they mature, they are myocytes.
152
Describe the order of development of cells in myogenesis.
* Progenitor cells (from dermamyotome of somites)
* Myoblasts
* Myotubes
* Myocytes
153
What is the difference between myocytes, muscle fibres and myofibres?
They are all the same. They are different names for a muscle cell.
154
Describe the smaller structures found within myocytes. (i.e. what makes up what makes up what)
* Myofilaments make up myofibrils
* Myofibrils make up myofibres (muscle cells)
155
Describe the number and location of nuclei in skeletal muscle cells.
* Multiple nuclei
* Located peripherally
156
What is the diameter and length of skeletal muscle cells?
* 10-100μm diameter
* Up to 35cm long
157
What are satellite cells and where are they found?
* Regenerative cells
* Found on the outside of myocytes
158
What is a muscle fibre?
It is just another name for a skeletal myocyte (muscle cell).
159
Describe how blood supply exists in muscles.
* Blood vessels penetrate the muscle and form a rich capillary network
* Runs between and parallel to the muscle fibres
160
What are the two proteins that make up microfilaments? Which is thin and which it thick?
* Actin -\> Thin
* Myosin -\> Thick
161
What is a sarcomere?
Repetitive sub-units of contractile apparatus.
162
Draw the structure of a sarcomere. Include the names of the different zones.
* A band (dark) -\> All of the length of myosin filaments
* I band (light) -\> Just actin filaments
* Z line -\> Where actin attaches
* H band -\> Just myosin filaments
* M line -\> What myosin attaches to
163
What happens to the different zones in a sarcomere when it contracts?
* I (just actin) and H (just myosin) bands are reduced in size
* A (all of myosin) bands do not change size
164
How many actin filaments surround each myosin filament?
6
165
What are the 4 main contractile proteins in skeletal muscle?
* Myosin
* Actin
* Tropomyosin
* Troponin
166
In skeletal muscle, which contractile protein has heads?
Myosin
167
Describe the structure of myosin in skeletal muscle.
6 polypeptides twisted to form a fibre helix with globular end, which has ATPase activity and binds to actin.
168
Describe the structure of actin in skeletal muscle.
Globular protein which polymerizes into polymeric fibres and contains a myosin binding site .
169
What are tropomyosin and troponin? What is their function in skeletal muscle?
Tropomyosin:
* Fibre-like protein which wraps helically around the actin
* In relaxed muscle, tropomyosin blocks attachment site for myosin crossbridge, thus preventing contraction
Troponin:
* Calcium-sensitive globular protein complex attached to end of each tropomyosin molecule
* Ca2+ binds to troponin -\> Knocks tropomyosin off binding site (for myosin head) and initiates contraction cycle
170
Draw a diagram to show how actin, myosin, tropomyosin and troponin interact.
171
What molecule triggers contraction in skeletal muscle and how?
* Ca2+
* It binds to troponin, causing tropomyosin to be knocked off of actin, so myosin heads can bind and contraction can occur
172
Aside from actin, myosin, troponin and tropomyosin, what are some important proteins involved in a sarcomere of skeletal muscle?
* Titin
* Alpha-actinin
* Nuebulin
173
What is titin and what is its function?
* Protein that connects myosin to the Z-line (actin is just anchored to Z-line)
* It is responsible for the passive elasticity of muscle and maintains sarcomere structure
174
What is unusual about titin?
It is the largest protein in the human body.
175
What is another name for titin?
Connectin
176
What is alpha-actinin and what is its function?
Protein that anchors actin to the Z-line.
177
What is usually in a complex with alpha-actinin?
CapZ
178
What is nebulin and what is its function?
Actin-binding protein that regulates the length of actin.
179
Draw the structure of a sarcomere, showing these components:
* Actin
* Myosin
* Troponin
* Tropomyosin
* Nebulin
* Alpha-actinin
* Titin
180
What are the different energy sources used for muscular contraction? For what length of time can each be used?
* Stored ATP + creatine phosphate -\> 8-10 secs
* Glycolysis -\> 90 secs
* Aerobic respiration -\> 2 min+
181
What occurs in muscles when the body cannot produce ATP? Why?
* The actin and myosin cannot dissociate
* So rigor mortis sets in
182
What are the different classes of skeletal muscle?
* Type I -\> Slow twitch
* Type II -\> Fast twitch
* Type IIa -\> Intermediate between fast and slow
* Type IIb -\> Classic fast twitch
183
Compare the structure of slow and fast twitch skeletal muscle.
* Slow twitch -\> Abundant mitochondria and extensive blood supply
* Fast twitch -\> Abundant glycogen
184
Compare how slow and fast twitch skeletal muscles can be distinguished histologically.
* Type I (slow twitch) -\> Succinate dehydrogenase stains more intensely
* Type II (fast twitch) -\> mATPase stains more intensely
185
What are T-tubules?
Invaginations of the sarcolemma (of myocytes) that surround myofibrils.
186
Describe the arrangement of T-tubules and the sarcoplasmic reticulum in skeletal muscle cells.
* T-tubules are invaginations of the sarcoplasmic reticulum that surround myofibrils
* Each T-tubule is flanked by two terminal cisternae of the sarcoplasmic reticulum (forming a triad):
* Impulse is conveyed from T tubules to cisternae
* Triggers Ca2+ release
* Troponin binds to it and activates actin & myosin
187
What are motor end plates?
Another name for neuromuscular junctions.
188
What is a motor unit?
* One motor neuron can supply many muscle cells
* Together, these form a motor unit
* Can contract in unison much faster than if each muscle cell individually stimulated
189
Describe briefly synaptic transmission at an NMJ.
* Nerve action potential opens voltage-gated calcium channels.
* Entry of Ca2+ triggers fusion of synaptic vesicle containing acetylcholine (ACh) with plasma membrane.
* Ach binds to AChR, causing opening of postsynaptic channels on muscle cell
* This triggers an action potential
190
What are fascicles?
Bundles of muscle fibres (muscle cells) groups together by perimysium.
191
What is the order of the connective tissues that are found in skeletal muscle?
Inner to outer:
* Endomysium
* Perimysium
* Epimysium
192
What is the endomysium and what does it surround?
* Surrounds each muscle fibre
* Composed of reticular fibres and external lamina (basal lamina)
193
What is the perimysium and what does it surround?
* Surrounds bundles (fascicles) of muscle fibers
* Dense collagenous connective tissue derived from epimysium
194
What is the epimysium and what does it surround?
* Surrounds entire muscle
* Dense irregular collagenous connective tissue
195
What is the function of the endomysium, perimysium and epimysium in muscle?
The collagen transmits mechanical force generated from contraction.
196
What is dystrophin, what is it part of and what is the function? [IMPORTANT]
* Dystrophin is a rod-shaped protein inside muscle cells
* It is a vital part of the dystrophin-associated glycoprotein complex (DGC)
* This complex anchors the cytoskeleton of the muscle fibre to the surrounding extracellular matrix, maintaining the mechanical integrity of the cell
197
What is muscular dystrophy and what causes it?
* Mutations in dystrophin gene (frame shift) -\> Leads to a truncated unstable form of dystrophin
* Absence of dystrophin leads to impairment of sarcolemma
* Force is no longer transmitted from myocytes to bones, so there is reduced movement at joints
* Symptoms: Muscle weakness and wasting
198
When does muscular dystrophy onset?
2 to 6 years
199
What is the inheritance pattern of muscular dystrophy?
X-linked recessive
200
Are there different isoforms of dystrophin?
Yes, because the gene is very long as has many introns.
201
What are the most common mutations causing muscular dystrophy?
* 60-65% deletions (these occur in hotspots)
* 5-15% duplications
* Point mutations
202
What are some treatments for muscular dystrophy?
* Corticosteroids
* Physiotherapy
* Cardiac + Respiratory support
* Palliative care
* Genetic counseling
203
What are some novel treatment methods for muscular dystrophy?
* Delivery of normal dystrophin gene
* Hard to do because:
* Size of dystrophin
* Needs to be delivered to all muscles
* Utrophin upregulation
* Utrophin is a closely related gene to dystrophin
* Expression is more tightly regulated -\> Only in immature muscle and at NMJ
* Can identify drugs/small molecules to activate utrophin promoter and allow functional replacement of dystrophin
* Exon skipping – anti-sense oligonucleotides
* Chemically modified single-stranded nucleic acids are used
* Hybridise to unique sequence of mRNA
* This is used to alter the exons are revert to the normal frame (since DMD is caused by frame shift)
204
What are the general symptoms of neuromuscular diseases?
* Spasticity or paralysis
* Depending on location & nature of problem
205
What are some examples of neurological disorders?
* Motor neuron disease
* ALS
* Cerebrovascular accident (stroke)
* Parkinson's disease
* Myasthenia gravis
206
Describe how satellite cells allow for skeletal muscle repair.
207
Is cardiac muscle striated?
Yes
208
What is cardiac muscle derived from embryologically?
Defined mass of splanchnic mesenchyme and myoepicardiaum mantel.
209
Draw the different layers of the heart wall.
210
What does the endocardium derive from?
Vascular endothelial progenitors
211
In the heart muscle, the cardiac myocytes are arranged in layers. What are these called?
Laminae
212
What is unusual about the shape of cardiac myocytes?
They are branched.
213
How many nuclei do cardiac myocytes have?
Single, centrally-located nucleus (usually)
214
Do cardiac myocytes have T tubules?
Yes
215
What is the distinguishing characteristic of cardiac muscle in histology?
The presence of dark transverse lines between cells -\> These are intercalated discs.
216
What are intercalated discs?
Structures that interface between adjacent cardiac muscle cells and support synchronised contraction.
217
What are the 3 components of intercalated discs?
* Desmosomes
* Adherens junctions
* Gap junctions
218
What is the function of desmosomes in intercalated discs between cardiac myocytes?
Bind cells together.
219
What is the function of adherens junctions in intercalated discs between cardiac myocytes?
Act as anchoring sites for actin filaments.
220
What is the function of gap junctions in intercalated discs between cardiac myocytes?
Provide continuity between adjacent cells and allow ions to pass between cells.
221
What is another name for adherens junctions in intercalated discs?
Fascia adherens (a.k.a. hemi Z-bands)
222
What is another name for desmosomes in intercalated discs?
Macula adherens
223
Overall, what do intercalated discs allow?
They allow cardiac muscle to act as a functional syncytium.
224
Summarise simply the structure and functioning of cardiac myocytes.
Branching mesh of mononuclear striated cells joined and electrically coupled by intercalated discs (desmosomes and gap junctions: electrically a 'functional syncytium').
225
What is meant by cardiac muscle being myogenic?
It is self-excitable.
226
Describe briefly excitation-contraction coupling in cardiac myocytes [EXTRA - this is more of a P&P topic].
227
Here is a section of muscle. What type of muscle is it and what do the letters a, d and g show?
Cardiac muscle (since this is an intercalated disc):
* a = Adherens junction
* d = Desmosome
* g = Gap junction
228
What are Purkinje fibres made of?
Modified cardiac muscle cells
229
Where are Purkinje fibres located?
* In inner ventricular walls
* Run beneath endocardium
230
What do Purkinje fibres enable?
Synchronised contractions of ventricles
231
How do Purkinje fibres appear histologically?
They have a pale-staining cytoplasm.
232
What are some structural differences between Purkinje fibres and normal cardiac myocytes?
* Rich in glycogen & mitochondria
* Contain limited contractile elements
* No T-tubule system
233
What is DCM? [EXTRA?]
234
What is HCM? [EXTRA?]
235
Are cardiac myocytes repaired?
* They are very slowly turned over with age
* Less than 50% of cardiomyocytes are replaced during a normal life span
236
Are smooth muscle cells striated?
No
237
How many nuclei do smooth muscle cells have?
They are mononucleate.
238
Describe and draw the shape of smooth muscle cells.
They are fusiform: elongated cells that taper at either end.
239
What are smooth muscle cells surrounded by?
* Basal lamina and network of reticular fibers.
* However, these layers are much thinner and therefore not as well seen as in skeletal muscle
240
Describe the alignment of contractile filaments in smooth muscle cells.
They are not arranged parallel, but instead form a sort of lattice.
241
Do the filaments in smooth muscle work in the same way as in striated muscle (skeletal and cardiac)?
Yes, they still work by sliding past each other, even though they are not arranged in a regular parallel manner.
242
In smooth muscle, actin and myosin are arranged in a...
Lattice
243
What are two important attachment points in smooth muscle?
* Focal densities
* Dense bodies
244
What do focal densities do in smooth muscle cells?
Attach actin filaments to the sarcolemma.
245
What do dense bodies do in smooth muscle cells?
Attach actin filaments to each other -\> They help maintain their alignment.
246
What are dense bodies functionally analogous to?
Z-lines
247
Draw a diagram to show the different contractile proteins and attachment points in smooth muscle cells.
248
What are invaginations of the sarcolemma called in smooth muscle cells?
Caveolae -\> These are functionally analagous to T-tubules.
249
What is the function of caveolae in smooth muscle cells?
* Involved in fluid and electrolyte transport (pinocytosis)
* Transmit depolarisation signalto inside the cell
250
What connects different smooth muscle cells?
Gap junctions -\> Couple adjacent cells chemically and electrically.
251
Compare how cells are connected in skeletal, cardiac and smooth muscle.
* Skeletal -\> Cells are long and multinucleate so they aren't really functionally connected in a significant way
* Cardiac -\> Intercalated discs (made of gap junctions, adherens junctions and desmosomes)
* Smooth -\> Gap junctions
252
Where is smooth muscle found?
Found in lining of viscera in:
* Gut
* Bladder
* Uterus
* Respiratory system
* Blood vessels
253
Compare the arrangement of smooth muscle cells in the uterus and bowel.
* Uterus -\> Loosely arranged
* Bowel -\> Regularly arranged
254
Describe the two functional arrangements of smooth muscle.
* Single unit
* Function as a unit enabled by electric coupling via gap junctions
* Allows muscle to behave as syncytium
* Multiunit
* Each cell isolated & stimulated independently to enable finer control
255
Give an example of an organ that includes single-unit smooth muscle.
* GI tract
* Bladder
256
Give an example of an organ that includes multi-unit smooth muscle.
* Iris of the eye
257
Describe the organisation of smooth muscle in the GI tract.
258
Label this. What muscle type is it?
259
What are the two forms of innervation that can trigger smooth muscle contraction?
* Release of neurotransmitter from autonomic varicosities (not NMJs)
* Visceral muscle pacesetters can spontaneously trigger contraction
260
Does smooth muscle feature motor units?
No, because they are innervated by autonomic varicosities, not NMJs.
261
What are some diseases related to smooth muscle?
262
Can smooth muscle cells regenerate?
Yes, they retain the highest capacity to regenerate of all the muscle types.
263
What are the two main ways in which smooth muscle can regenerate?
* Smooth muscle cells retain ability to divide, and can increase in number this way
* New cells can be produced by the division of pericytes that lie along some small blood vessels
264
Can smooth muscle hypertrophy?
Yes
265
What cells wrap around smooth muscle and what is their function?
Pericytes -\> Help regenerate the smooth muscle.
266
What types of myocyte are these?
267
What makes up gap junctions in cardiac muscle? How are they regulated?
* Several connexins join to form a connexon
* Two connexons form a gap junction
* These can be regulated by phosphorylation and calcium
268
Are gap junctions selective?
No, but they can be regulated by phosphorylation and calcium.
269
Draw the process of formation of gap junctions. [EXTRA]
270
