20-01-21 - Smooth Muscle Contraction Flashcards
What are the 7 places smooth muscle is found?
1) Blood vessels
* Regulates lumen diameter
* Contributes to maintenance of blood pressure
2) Digestive tract
* Rhythmic peristalsis propels food
3) Bladder wall/urinary tracts
4) Respiratory tract
5) Reproductive tract
6) Eyes
7) Skin
Where is smooth muscle normally found in organs?
*With the exception of the heart, muscle in all of the walls of the hollows organs is typically smooth muscle
What are the two types of smooth muscle?
What advantage does thus electrical isolation of cells have?
How are these cells stimulated to contract?
What are 4 examples of where multi-unit smooth muscle is located?
- The two types of smooth muscle multi-unit smooth muscle or unitary (or single unit) smooth guys
- This electrical isolation of cells allows for finer motor control
- These cells are typically stimulated to contract by neurons, whereas other muscle can be stimulated by multiple chemicals
- Examples of where multi-unit smooth muscle is located:
1) Ciliary muscle of the eye
2) The Iris
3) Piloerector muscles
4) Vas deferens
How do multi-unit smooth muscle cells contract since they receive their own branch of an autonomic neuron?
These cells contract independent from one another
What do each of these multi-unit smooth muscle cells receive?
Each of these cells receive their own branch of an autonomic neuron
What does multi-unit smooth muscle consist of?
Multi -unit smooth muscle consists of discrete/separate cells
What advantage does thus electrical isolation of cells have?
This electrical isolation of cells allows for finer motor control
What does unitary (single unit)/ visceral consist of?
How do these cells contract?
How are they stimulated to contract?
What is the most common smooth muscle fibre?
What are 5 example of where unitary smooth muscle is found?
- Unitary/visceral smooth muscle consists of sheets of electrically coupled cells
- These cells contract in unison
- They are all stimulated to contract by a single neuron, resulting in contraction in unison, so that who whole organ synchronises its contraction
- The most common form of smooth muscle fibre is unitary muscle
• Examples of where unitary smooth muscle can be found:
1) GI tract
2) Bile ducts
3) Ureters
4) Uterus
5) Blood vessels
How are the actin and myosin filaments arranged in smooth muscle?
Does smooth muscle have striations?
What do dense bodies correspond to?
What is their structure like?
What is their 2 roles?
What are dense bodies composed of?
What is the role of gap junctions in smooth muscle?
What are 3 key differences in smooth muscle structure compared to skeletal and cardiac muscle?
• Actin and myosin filaments are arranged diagonally along fibres, and are less regularly organised
• Smooth muscle does not have striations
• Dense bodies of smooth muscle correspond to Z -discs of skeletal and cardiac muscle
• Dense bodies are a lattice like structures
• They anchor actin within the fibre and tether contractile proteins to the sarcolemma
• They are also responsible for transmitting forces of contraction within and between cells, which allows for contraction in unison
• Dense bodies are composed of intermediate filaments such as :
1) Α-actinin
2) Desmin
3) Vimentin
- Gap junctions electrically couple cells in unitary smooth muscle
- Focal adhesions connect cells together mechanically
• Differences in structure between smooth and cardiac/skeletal muscle:
1) No troponin in smooth muscle and no tropomyosin covering myosin binding sites – regulation of smooth muscle contraction differs to both skeletal and cardiac muscle
2) No t-tubules in smooth muscle – no invagination of the cell membrane to pass the electrical current into the cell
3) The SR is much less developed in smooth muscle
How is the SR arranged in smooth muscle cells?
What does this mean for the amount of calcium can be held in the cell?
What is released form the SR?
What is the main trigger for contraction?
What are caveolae?
How are they linked to the SR?
What do they contain?
What do SR and caveolae do together?
- In smooth muscle cells, the SR is largely associated with the sarcolemma and not clearly aligned with myofilaments
- With far less SR, this means far less ability of smooth muscle cells to hold calcium in the cell compared to cardiac and skeletal muscle cells
- Calcium is released from the SR, but it is not the main source of contraction
- Extracellular calcium is the amin trigger from contraction, which is similar to cardiac muscle
- Caveolae are pouch like infoldings of the sarcolemma of smooth muscle cells
- Caveolae can be considered as rudimentary t-tubules
- Caveolae contain large numbers of Ca2+ channels
- Caveolae and SR will both initiate the flow of calcium into the cytosol to trigger the next step in the events of contraction
What is the role of calcium in smooth muscle cells?
What are the two sources of calcium that contribute to this?
What are the 3 mechanisms that lead to an increase in cytoplasmic calcium concentration?
What is triggered when calcium concentration in cytoplasm increases?
What else may also enhance this?
• Calcium is still the key molecule involved in couple the electric signal in the form of an action potential into a mechanical contraction
• The two sources of calcium that contribute to this are:
1) The SR
2) Extracellular Ca2+ influx
• After an action potential has been delivered, three mechanisms lead to an increase in cytoplasmic calcium concentration:
1) Voltage gated L-type Ca2+ channels
• Leading to calcium induced calcium released (CICR) via ryanodine receptors on the SR
2) Receptor operated Ca2+ channels
• (RRCC) leading to IP3 receptor activation and CIRC
3) Store operated Ca2+ channels (SOC)
- As calcium concentration in the cytoplasm increases, it causes a space, which has a knock-on effect to receptors of the cell membrane, allowing or more extracellular calcium to flow into the cell
- Agonists may also enhance the release of calcium e.g chemical messengers binding to G-protein couple receptors
How is myosin in smooth and cardiac/skeletal muscle similar?
How does the myosin in smooth and skeletal/cardiac muscles differ?
What does vascular/GI tract smooth muscle actin consist of?
What is the role of Calmodulin?
What is not present in smooth muscle?
- The tertiary structure of myosin in smooth muscle is similar to that of skeletal/cardiac muscle
- Myosin in smooth and cardiac/skeletal muscle is different:
1) Amino acid sequence
2) Arrangement of myosin heads
• Along the entire length of the muscle
• Head hinges opposing direction on the same filament
• This results in pulling in opposite directions, increasing shortening
• Up to 80% in smooth muscle, compared to 30% in cardiac/skeletal
3) Myosin in smooth muscle needs to be phosphorylated before it can interact and form cross-bridges with actin
• Smooth muscle actin consists of:
1) α-SMA – vascular
2) γ-SMA – GI tract
• Calmodulin is the key regulatory protein enabling myosin to interact with actin (troponin stand in for skeletal muscle – no troponin in smooth muscle)
Describe the 6 steps of smooth muscle contraction.
Is there any other regulatory aspect needed?
• Process of smooth muscle contraction
1) Smooth muscle contraction is initiated by calcium influx from extracellular and SR
2) 4 calcium bind to calmodulin (instead do troponin as in skeletal muscle), activating it
3) Calmodulin can now become an activator of a myosin light chain kinase (MLCK)
4) Ca-calmodulin-MLCK complex leads to phosphorylation of the hinge region of the myosin head (Myosin light chain – MLC)
5) Phosphorylated myosin head binds to actin, and the power stroke occurs automatically
6) A second ATP is required to release myosin head from actin
• There are no other regulatory aspects needed, except the action potential and calcium in the cytoplasm to begin with
Describe the 4 steps of smooth muscle relaxation.
What is the time for relaxation determined by?
How does the time for relaxation compare in smooth muscle cells to skeletal/cardiac muscle cells?
• Steps of smooth muscle relaxation:
1) Wen the stimulus ends, calcium is pumped out of the cell or into the SR
2) When calcium drops below a critical level, calcium dissociates from calmodulin, which inactivates MLCK
3) Myosin phosphatase removes phosphate from the MLC, causing detachment of the myosin head from the actin filament
4) This causes relaxation
- The time for relaxation in smooth muscle is determined by the amount of active myosin phosphatase in cells
- Typically, smooth muscle contracts at far slower rates than skeletal/cardiac cells
Where is calcium transported to after contraction?
What are the 3 ways this is done?
Why is this done?
What senses the calcium levels in the SR?
What does this activate?
Where does this occur?
- After contraction, calcium is transported out of the sarcoplasm and into the extracellular fluid or into the SR
- This is done via:
1) Membrane Ca2+ ATPase (active)
2) Ca2+ ATPase (SERCA) (active)
3) Na+ - Ca2+ exchangers (passive)
- This is done to ensure sufficient calcium is returned to the SR
- Stim1 senses calcium levels in the SR
- It can then activate store-operated Ca2+ channels (SOCs) for the influx of calcium back into the SR, which enables the SR to refill
- This occurs at specialised regions where SR encounters the sarcolemma
What do smooth muscle cell membranes contain that skeletal muscle cell membranes?
What does smooth muscle lack that is seen in skeletal muscle?
What do autonomic nerve fibres create?
What are varicosities?
What do they release?
How does the unitary muscle compare with the multi-unit muscle?
What may happen to the layers in unitary smooth muscles?
- Unlike skeletal muscle cells, smooth muscle cell membranes contain receptors which can initiate or inhibit contraction
- Smooth muscle lacks highly specialised neuromuscular junctions, as seen in skeletal muscle
- Autonomic nerve fibres branch diffusely, creating wide synaptic clefts called diffuse junctions
- Varicosities are swellings that release neurotransmitters in the general area of smooth muscle cells, which diffuse across the diffuse junctions and hit receptors, initiating action potentials in the smooth muscle cell
- In unitary muscle, it is not as individual as it is in the multi-unit, where they all receive their own individual stimulation from the autonomic neuron
- Sometimes, the neurotransmitter may only associate with the top layer of cell, and relies on the gap junctions and excitation to spread through to the lower muscle cells
Where may varicosities from a single axon be located?
Where do varicosities originate?
How many cells can be affected by how many neurons and vice versa?
How close are varicosities in multi-unit smooth muscle?
What is this like?
How many cells do neurotransmitters target in multi-unit smooth muscle?
What are the 2 main neurotransmitters used in smooth muscle?
- Varicosities from a single axon may be located along several muscle cells
- Varicosities originate from postganglionic fibres of both sympathetic and parasympathetic neurons
- Several smooth muscle cells are influenced by neurotransmitters released by a single neuron
- A single smooth muscle cell may also be influenced by neurotransmitters from more than one neuron
- In multi-unit smooth muscle, varicosities are in much closer contract, and much more like neuromuscular junctions
- When neurotransmitters are release in multi-unit smooth muscle, they will be targeting an individual cell they are intended for, which allows for finer control e.g focus in ciliary muscle of the eye
- Neurotransmitter’s acetylcholine or noradrenalin are used in smooth muscle, which can be excitatory or inhibitory
What can neurotransmitters do to contractile activity?
What might the same neurotransmitter produce?
What affects does noradrenaline stimulate?
What is the type of response dependent on?
- Neurotransmitters can either stimulate or inhibit contractile activity
- The same neurotransmitter may produce opposite effects in different smooth muscle tissues
- Noradrenaline stimulates contraction of most vascular smooth muscle by acting on α-adrenergic receptors
- It also produces relaxation or airway (bronchiolar) smooth muscle by acting on β2-adrenergic receptors
- The type of response (excitatory or inhibitory) depends on the receptors the chemical messenger binds to in the target cell membrane
What are 5 things that can initiate smooth muscle contraction?
What does this allow for?
• Smooth muscle contraction can be initiated by:
1) ANS stimulation
2) Spontaneous electrical activity from the neurone
3) Stretch
4) Hormones
5) Local chemicals within the extracellular fluid:
• Oxygen
• Carbon dioxide
• Acidity
• Ion concentration
• Nitric acid
• This allows for fine turning of activity in response to the environment
How does smooth muscle resting membrane potential compare with that of skeletal muscle?
What does this make smooth muscle?
What 3 things can an action potential in a smooth muscle cell be?
What 4 things can unitary smooth muscle spikes be generated by?
What is mainly responsible for the membrane potential in smooth muscle?
What leads to elongation of contraction?
- Smooth muscles resting membrane potential is -50 to -60mV, which is around 30mV less negative than skeletal muscle at around -80mV
- This makes smooth muscle more excitable
• An action potential in a smooth muscle can be:
1) A simple spike
2) Spikes on top of slow waves
3) Spike followed by a plateau (similar to those seen in cardiac tissue)
• Unitary smooth muscle spikes can be generated by:
1) Electrical stimulation
2) Hormones
3) Stretch
4) Spontaneous depolarisation from pacemaker cells (interstitial cells) of the intestinal wall
- Calcium is mainly responsible for membrane potential in smooth muscle – slower to open and close than Na+ channels
- Binding of actin and myosin is slower, leading to elongation of contraction in smooth muscle
How long is smooth muscle contraction?
What 2 things is this due to?
How does force of contraction in smooth muscle compare with that of skeletal and cardiac muscle?
How is prolonged (tonic) contraction enabled?
When does it occur?
What is needed for this to occur?
• Smooth muscle contraction is prolonged, lasting minutes, hours or even days (tonic contraction)
• This is due to:
1) Slower ATPase activity from myosin, leading to slower cross-bridge formation between actin and myosin
2) Slower influx of Ca2+ ions (in comparison to skeletal and cardiac muscle)
- The force of contraction in smooth muscle is often greater than that of skeletal or cardiac muscle
- This is due to the longer cross bridge attachments between actin and myosin
- Prolonged (tonic) contraction is made possible with the latch mechanism, which maintains prolonged contraction with minimal ATP use – only 1 ATP for each cycle
- This occurs when myosin becomes dephosphorylated while still attached to the actin
- This only happens if cytoplasmic calcium concentration remains elevated among background levels
Comparisons of different muscle types
How large are smooth muscle cells?
How are they organised?
Do they have striations?
How many nuclei do they have?
Are they under voluntary or involuntary control?
What 3 things can they be controlled by?
How is smooth muscle organised in the intestinal tract?
- Smooth muscle cells are small – about 100-200µm in length
- They are spindle shaped cells arranged in sheets that are perpendicular to each other, and are less regularly organised
- Smooth muscle cells do not have striations
- They have a single nucleus
- They are under involuntary control
• Smooth muscle cells can be controlled by:
1) Autonomic Nervous System
2) Hormones
3) Stretch
• Smooth muscle in the intestinal tract is arranged in longitudinal and circular layers
