BL L14 Flashcards
Common characteristics between smooth muscle and cardiac muscle
- Nuclei are central not peripheral
- Only one contractile cell type (cardiac muscle - cardiomyoctye, smooth muscle - smooth muscle type)
- Act as a syncytium (wave-like function)
- Myocytes communicate through gap junctions - (cardiomyocytes - intercalated disk)
Difference between smooth muscle and cardiac muscle
- Smooth muscle does not contain sarcomeres
- Electrical conduction - specialised cells/routes in cardiac muscle
- No troponins in smooth muscle (this is because smooth muscles do not have sacromere)
What type of muscle is this?
Cardiac muscle
What type of muscle is this?
Smooth muscle
Role of the sympathetic nervous system with heart rate -
Sympathetic - increase heart rate
Role of the parasympathetic nervous system
Parasympathetic nervous system - slow the heart down
Where does the sympathetic nerve come from and which part of the heart does it act on?
Comes from T1-T4 on the spinal cord, acts on the atria and ventricles
Where does the parasympathetic nerve come from and which part of the heart does it act on?
From modulla oblongata, only acts on the atrium
How does the contraction occur in the heart?
- Electrical signal sent through node
- Electrical signals acts on the membrane, it passes through the T-tubules
- Activates the DHP receptor on the membrane
- DHP receptor pumps Ca2+ ions into the sacroplasmic reticulum
- This activates the RyR to pump Ca2+ ions from the SR in muscle cells, so the Ca2+ can interact with the contraction machinary in the sacromere.
- Tropomyosin sits on the surface of actin. Three toponin molecules (TN-I, TN-C, TN-T). When Ca2+ ions bind to TN-C, the TN-C pulls the tropomyoosin away from the actin molecules, the actin binding site is now exposed
etc. ..
Reminder of smooth muscle cell ultrastructure
When the myosin and actin in the cytoplasm recieve a singal to contract, they join up with dense bodies…
When does contraction stop?
When Ca2+ stop binding to troponin C
Meaning of innervating muscles
To stimulate
Where does the innervation of skeletal muscles take place?
Neuromuscular junction
What are the main components of a neuromuscular junction?
- Synaptic knob, which is the dilated tip of a nerve fibre that contains synaptic vesicles
- Synaptic cleft, which is the intercellular space between the end of the nerve and the muscle cell
- Synaptic vesicle that contains neurotransmitter
- Acetylcholine (ACh), the neurotransmitter
- Junctional folds within the sarcolemma increase the surface on the distal side of the motor end plate and have
- The acetylcholine (Ach) receptor on the surface of Junctional folds closest to the nerve bouton to which Ach binds
- The enzyme acetylcholinesterase (AChE), which resides in the synapse, usually at the base of the junctional folds is next to a high concentration of channels for the Na+ ion, that speed up conduction of the electrical charge (action potential)
How is the neurotransmitter released at the axon bouton?
- The change in electrical polarity in the membrane of the axon bouton causes the movement of Ca2+ ions into the axon bouton
- The influx of CA2+ causes Ach to be released through exocytosis (vesicles containing Ach fuse with the sarcolemma) releasing the Ach into the synaptic cleft.
Where is the motor end plate?
What is the significancce of innvervation ratio?
What are kranocyte cells?
- The kernocyte cell sits over the top of the terminal (last) Schwann cell
- Scientists are unsure of it’s function but it may holds the end of the nerve in place to the muscle fibre
- Motor nerve terminal sits in the motor end plate
Describe the steps leading to contraction of skeletal muscles
- Initiation: nerve impulse along motor neuron axon arrives at neuromuscular junction
- Impulse prompts release of acetylcholine (Ach) into synaptic cleft causing local depolarisation of sarcolemma
- Voltage-gated Na+ channels open; Na+ ions enter cell
- General depolarisation spreads over sarcolemma and into T tubules
- Voltage sensor proteins of T tubule membrane change their conformation
- Gated Ca2+ ion-release channels of adjacent terminal cisternae are activated by step 5.
- Ca2+ ions are rapidly released into the sarcoplasm
- Ca2+ binds to the TnC subunit of troponin and the contraction cycle is initiated
- Ca2+ ions are returned to the terminal cisternae of sarcoplasmic reticulum
What is myasthenia gravis?
Autoimmune disease as bodies antibodies, bind to the Ach receptor and destroy it (after destroying the Ach receptors, the enzymes that were involved, located themsevles at the bottom of the clefts)
• 30% reduction in receptor number sufficient for symptoms
• Leads to reduction in endplate ‘invaginations’ in synaptic clefts
• As invaginations are lost, leads to reduced synaptic transmission
Symptoms:
• Intermittent muscle weakness
drooping of one or both eyelids (ptosis)
• blurred or double vision (diplopia) due to weakness of the muscles that control eye movements
• a change in facial expression
• difficulty swallowing
• shortness of breath
• impaired speech (dysarthria)
• weakness in the arms, hands, fingers, legs, and neck
See pic of end plate
Myasthennia gravis end plate (diagram)
Recap - parts of a scromere
Myosin and actin - describe their structure
Myosin:
- An individual myosin molecule has a rod-like structure from which two ‘heads’ protrude
- Each thick filament consists of many myosin molecules, whose heads protrude at opposite ends of the filament
Actin:
- Actin has two protein components: F-actin fibres G-actin globules
- Tropomyosin-troponin complex sits over binding sites
Describe actin and the other molecules it is associated with in more detail
- Actin
- Tropomyosin
- Troponin complex: TnC, TnI, TnT
Describe the structure of the contraction unit (both skeletal and cardiac muscle)
- Tropomyosin molecules coil around the actin helix, reinforcing it
- A troponincomplex is attached to each tropomyosin molecule
- In the centre of the sarcomere, the thick filaments are do not have of myosin heads (H band)
- The myosin heads extend towards the actin filaments in regions of potential overlap
What is the role of Ca2+ in the contraction mechanism?
- As Ca2+ binds to TnC of troponin, a conformational change moves tropomyosin away from actin’s binding sites
- This allows myosin heads to bind actin, and contraction begins
- The tropomyosin sits in the cleft of the G-actin ‘spheres
Describe the events that occur after the Ca2+ has bound to TnC and the tropomyosin has moved from the binding site…
Few points to make it clear -
Step 2. The release of ADP+P causes the myosin head and actin filament to move relative to each other (working stroke)
Step 3. New ATP attaches to the mysoin head, the cross bridge detaches
Step 4. ATP is split into ADP+PI, cocking the head of the myosin
Lengths of the actin and myosin during muscle contraction
- The lengths of the actin and myosin filaments always remain the same!
- The sarcomeres shorten
- Z lines come closer to each other
Summary slide from Ach being released from the axon -> Ca2+ uptake into the sacroplasmic reticulum after contraction
What is a muscle insertion?
- Structure the muscle attaches to
- Tends to be moved by contraction
- Tends to be distal
- May be bone, tendon or connective tissue (usually tendon to bone).
- Greater motion than origin during contraction.
Name and describe each type of biomechanical lever
- First class lever e.g. see-saw: Effort at one end load at other, e.g. Extension/flexion of head, Not many examples in the body
- Second class lever e.g. wheelbarrow: Effort at one end, fulcrum at other, e.g. Plantar flexion of foot
- Third class lever e.g. fishing rod: Effort between load & fulcrum, mechanical disadvantage, most common in body
NB: falcrum is the pivot point
Muscle compartments
- Muscles with similar actions grouped together
- Surrounded by thick dense fascia
- Compartments Based on location - Anterior, Posterior, Lateral, Medial
e.g. the top and bottom picture - show all the upper arm muscles are split into two comparments and working together (one compartment - bicep branchi, branchilis etc, second compartment - triceps)
Compartment syndrome - what is this? symptoms? treatment?
- Each group of muscles in the arms and legs, together with nearby blood vessels and nerves, is contained in a space surrounded by tissue called fascia.
- Trauma in one compartment could cause internal bleeding in this compartment, which exerts pressure on blood vessels and nerves. This restricts the blood flow to the area and is potentially damaging to the muscles and nearby nerves.
- Fascia does not stretch, therefore the pressure in the compartment greatly increases
Symptoms:
• Deep constant poorly localised pain
• Aggravated by passive stretch of muscle group
• Paresthesia (altered sensation e.g., “pins & needles”)
• Compartment may feel tense and firm.
• Swollen shiny skin, sometimes with obvious bruising.
• Prolonged capillary refill time
Treatment (acute):
Fasciotomy - open up the superficial fascia around this compartment. When damage is released, perfom a skin graft.
What is muscule tone and muscle strength? How are muscles regulated?
Muscle tone = the tension in a muscle at rest, ability to respond to activity
Muscle stength = the muscle’s ability to contract and create a force in response to resistance
Regulated by:
• Motor neuron activity
• Muscle elasticity
• Use
• Gravity
More info on muscle tone:
• Healthy muscles never fully ‘relaxed’
• Retain amount of tension and stiffness (muscle tone)
• Makes muscle ready to react
• Improves with exercise
The pic shows a man who has increased he muscle tone -
Muscle remodelling (caused by activity and inactivity)
- Continual - as using muscle all of the time
- Replacement of contractile proteins in 2 weeks
- Destruction > replacement = atrophy
- Replacement > destruction = hypertrophy (developing new fibres)
See seperate diagram on number of fibres and fascile size with atrophy and hypertrophy
What is the mechanism of hypertrophy?
Caused by: Overstretching such that the A and I bands can no longer re-engage
• New muscle fibrils are produced
• New sarcomeres are added in the middle of existing sarcomeres
• New muscle fibres arise from mesenchymal cells
• Over-stretching is thought to feature in some cardiac pathologies (i.e. enlarged ventricles)
Duchene muscular dystrophy (describe would should happen normally, describe what happens in DMD)
- Dystrophin is attached to the dystroglycan complex located on the myocyte membrane. Dystrophin links to dystroglycan complex, the dystrophin links to the actin. This linkage prevents the membrane being damaged when the muscle contracts.
DMD:
- Genetic mutation (X-linked recessive so males only) causes the dystrophin to be extremely short, often lacking the dystroglycan-binding end, making it dysfunctional
- Everytime a muscle contracts, small rips in the membrane occurs
- These small rips allows the diffusion of molecules into and out of the myocyte, for example, Ca2+ ions
- Ca2+ ions are in much higher conc outside of the membrane
- These rips allow the Ca2+ to enter to membrane, Ca2+ ions then activated inactive protease
- Normally these proteases would only break down non-functional proteins, however, in DMD, high calcium ions means there are too many of these proteases. They then start to break down important functional proteins. This kills the myocyte
- Creatine kinase and myoglobin leaks out of the cell (as myocytes are dying)
Diagnosising DMD: High creatine kinase in the blood
Symptoms:
Creakine kinase is the enzyme necessary for short-term energy storage in myocytes to use in contraction, less creatine kinase = less energy storage = muscle weakness.
Also myoctyes aren’t able to be regerenated at the same speed as you get older, as they are damaged and kill, instead fat and scar tissue fill in the gaps, leading to muscle weakening. Heart and diaphragm are muscles, these become so weak, they stop functioning = person dies.
Symptoms -
- Belly sticks out as weakened abdominal muscles
- Poor balance as can’t control posture
- Swollen calves - due to fat and scar tissue build up
- Walk on tip toes - contractive tendon
- Drag feet - can’t contract foot easily
- Knees bent - can’t take all weight
- Arms held behind body for balance
Visualise a muscle biopsy of someone with Duchene muscular dystrophy
Muscle cells replaced by adipose tissue
Troponin (what it is used in? why is it useful? why is it better than other indicators?)
Useful Diagnostic Tool
• Troponin (I & T forms) used as a marker for cardiac ischaemia (There are specific isoforms of cardiac I & T forms)
• Released from ischaemic cardiac muscle within an hour
• Must measure within 20 hours for absolute accuracy
• The smallest changes in troponin levels in the blood are indicative of cardiac muscle damage
• Quantity of troponin is not necessarily proportional to the degree of muscle damage
• Used by many Emergency Departments as the assay of choice, superseding muscle enzyme assays (i.e. instead of creakine kinase)
• Levels of troponin stay high in the blood for days (troponin T up to 14 days!), whereas creatine kinase is out of the blood in 2 days - see graph
How does botulism toxin and botox work?
- Toxin produced by Clostridium botulinum (a bacteria)
- Blocks neurotransmitter release at the motor end plate
- Causes non-contractile state of skeletal muscle - Flaccid paralysis (as neurotransmitter is not released)
- Clinically used to treat muscle spasms (e.g. cervical dystonia)
- Used cosmetically to treat ‘wrinkles’
What is primary toxin uptake referring to? what is happening? what affect may this have?
Botulism toxin and botox
Botulism toxin can be taken up by the nerve, transported through axons to other nerves and to the CNS, it can cause some brain disorders (if it reaches the brain)
Organophosphate poisoning (what is this? what does it affect? Symptoms?)
- Organophosphates are used as pesticides
- Inhibits the normal function of Ach esterase
- Ach activity at the neuromuscular junction is potentiated
- Leads to multiple symptoms and signs (Effects on both somatic and autonomic signalling)
Muscarinic symptoms (if OP inhibits Ach esterase at these receptors): SLUDGE
S - Salivation (more saliva)
L - Lacrimination (increase tears)
U - Urination (urinate more)
D - Defecation (defecate more)
G - GI cramping
E - Emesis (vomit)
Nictoninic symptoms: Monday, Tuesday, Wednesday, Thursday, Friday
M - muscle cramps
T - Tachycardia (heart beats faster)
W - weakness
T - twitching
F - fasciculation (small contractions)
Malignant hyerthermia (what is it? symptoms?)
- Severe reaction to anaesthetics – Succinylcholine
- Autosomal dominant inheritance pattern - RyR1 gene Males>Females
- Don’t know you have this allergy until exposed to it
- Massive contractile fasciculation Muscle rigidity caused by ↑Ca2+ release
- Outcome – excessive heat and metabolic acidosis
- ↑Muscle breakdown and hyperkalaemia (high blood [K+])
- Mortality risk 5% with treatment; 75% without treatment
Caused by:
- RyR1 receptor isn’t working properly. This receptor is in the sacroplasmic reticulum membrane
- This allows lots of Ca2+ ions to exit the sacroplasmic reticulum into the cytoplasm
- The Ca2+-ATPase works really hard to take the Ca2+ ions back into the sacroplasmic reticulum, but the RyR is putting so much Ca2+ out, it can’t take all of it back in.
- This means the muscle contracts and contracts and contracts (muscle rigidity)
- As the muscle is continuously contracting, it produces lots of heart and CO2
- Lots of CO2 results in metabolic acidosis
- Metabolic acidosis causes muscle breakdown, releasing the contents of the muscle (e.g. K+, troponins, myoglobinc, creakine kinase)
- Lots of K+ causes hyperkalaemia
- Hyperkalaemia stops the cardiac muscle from contracting (death)
