Why aren’t smooth muscles studied as much as skeletal muscles? (5)
- highly variable in structure and function
- anatomy makes functional studies difficult
- controlled by hormones, paracrines, and neurotransmitters
- has variable electrical properties
- multiple pathways influence contraction and relaxation
How do smooth muscles compare with striated muscles? (6)
- much smaller fibres – around 250 long and 5 μM wide
- not arranged in sarcomeres
- has longer actin and myosin filaments
- much slower myosin ATPase activity
- myosin light chain plays regulatory role
- has very little sarcoplasmic reticulum – Ca2+ also enters cell from extracellular fluid
Describe the structure of smooth muscle.
- mononucleate, spindle-shaped cells
- no visible striations – thick and thin filaments are not organized into sarcomeres
- SR is less extensive than in striated muscle
- no t-tubules
- adjoining cells can be connected via gap junctions, but depends on muscle type
- orientation of cells in relation to each other differs in relation to the needed direction of contraction (ie. smooth muscles of the stomach vs. eye)
How are thick and thin filaments of smooth muscle organized? How does this differ from striated muscle?
bundles of thick and thin filaments are arranged into networks throughout the cytoplasm
- approximately 15 thin filaments for every thick filament
- adhesion plaques attach thin filaments to cell membrane
- thin filaments are anchored to dense bodies, which attach to cytoskeleton
thick and thin filaments are arranged into sarcomeres in striated muscle
Compare the contraction duration of skeletal, cardiac, and smooth muscle.
from fastest to slowest contraction duration:
skeletal > cardiac > smooth
How is smooth muscle contraction regulated?
- regulated by a variety of factors including sympathetic neurons, hormones, and stretch
- many of these factors regulate contraction via changes in cytoplasmic [Ca2+], although some regulation of contraction is achieved independent of Ca2+
- regulation of contraction can also be achieved by changing the sensitivity to Ca2+ rather than by changing [Ca2+]
- Ca2+ affects both thick and thin filaments
Contraction Regulation – Thick Filament
- Ca2+ enters cell and is released from SR, increasing intracellular [Ca2+]
- Ca2+ binds to calmodulin (CM)
- Ca2+-CM activates myosin light chain kinase (MLCK)
- activated MLCK phosphorylates the light chains in myosin heads, increasing myosin ATPase activity
- active myosin cross-bridges slide along actin, resulting in muscle tension
Contraction Regulation – Thick Filament
What role do thick filaments play in the regulation of smooth muscle contraction in vertebrates?
myosin must be activated before it can bind
- myosin light chain kinase (MLCK) phosphorylates the regulatory myosin light chain (MLC) – increases myosin-actin binding
Contraction Regulation – Thick Filament
What does myosin light chain kinase (MLCK) do?
phosphorylates the regulatory myosin light chain (MLC) – increases myosin-actin binding
Contraction Regulation – Thick Filament
What does myosin light chain phosphatase (MLCP) do?
dephosphorylates the regulatory myosin light chain (MLC) – deactivates/prevents myosin binding
Contraction Regulation – Thick Filament
What factors regulate MLCK and MLCP?
some pathways involve changes in [Ca2+], while others do not
- ie. nitric oxide (NO) induces smooth muscle relaxation via pathway that activates MLCP without changing [Ca2+]
Contraction Regulation – Thin Filament
Smooth muscle lacks troponin. How does tropomyosin function?
position of tropomyosin on the actin filament is regulated by caldesmon
Contraction Regulation – Thin Filament
How is the myosin binding site blocked in relaxed smooth muscle?
binding of both caldesmon and tropomyosin to actin
Contraction Regulation – Thin Filament
How does contraction occur?
- cytoplasmic [Ca2+] increases
- calmodulin binds Ca2+, then binds to caldesmon
- calmodulin-caldesmon dissociates from actin and tropomyosin, shifting position and exposing myosin binding sites which allows for contraction
Contraction Regulation – Thin Filament
How does relaxation occur?
- cytoplasmic [Ca2+] decreases
- Ca2+ dissociates from calmodulin
- caldesmon binds to actin
- tropomyosin shifts position to block myosin bindings sites which allows relaxation
Contraction Regulation – Thin Filament
What regulates caldesmon activity? How?
hormones
- many of the hormones that affect smooth muscle function act via signaling cascades that lead to phosphorylation or dephosphorylation of caldesmon
- ie. signaling cascade that leads to phosphorylation of caldesmon by MAP kinase – phosphorylated caldesmon will not bind to actin, even with low cytoplasmic [Ca2+]
How does Ca2+ regulate contraction via both thick and thin filaments?
- with increased cytoplasmic [Ca2+], calmodulin binds Ca2+
- Ca2+-calmodulin binds to caldesmon, causing it to detach from actin, exposing myosin binding sites on the thin filaments
- Ca2+-calmodulin binds to MLCK such that it phosphorylates the myosin light chain, activating the myosin of the thick filaments
What does the contraction and relaxation of vascular smooth muscle change? What does this affect?
changes vessel diameter
- allows regulation of the distribution of blood flow throughout the body
- contributes to regulation of blood pressure
Describe a hormone that affects vascular smooth muscle.
angiotensin
- hormone produced by the liver that increases blood pressure
- in vascular smooth muscle, angiotensin receptors are G protein-coupled receptors – when they bind angiotensin, they generate a signaling cascade that releases Ca2+ from SR, increasing cytoplasmic [Ca2+]
What are phasic smooth muscles?
muscles that contract in bursts triggered by APs that cause increased cytosolic Ca2+
- ie. gastrointestinal and urogenital systems
What are tonic smooth muscles?
muscles that are partially contracted at all times
- varies its contraction according to cytosolic Ca2+ level
- ie. large arteries and veins
What are two ways in which smooth muscle is organized?
- multi-unit smooth muscle
- single-unit smooth muscle
Describe multi-unit smooth muscles.
cells must each be separately stimulated by nerves to contract (myocytes are not electrically coupled with each other)
- found surrounding arteries, respiratory airways, and in the eye
- contractile activity is neurogenic and phasic
- can be initiated to contract by the autonomic nervous system and hormone signaling
- rarely contain gap junctions between cells
Describe single-unit smooth muscles.
muscle fibres are self-excitable and contract as a single unit
- more common arrangement found in walls of most visceral organs
- gap junctions electrically link neighbouring cells (functional syncytium)
- contractile activity is myogenic and may be phasic (pacemaker potentials) or tonic (slow-wave potentials)
- modified by autonomic nervous system
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Lecture 2: Cytoskeleton and Motor Proteins40
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Lecture 3: Striated Muscle28
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Lecture 4: EC Coupling (Striated Muscle)50
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Lecture 5: Skeletal vs. Cardiac (Striated Muscle)19
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Lecture 6: Paper 1 (Sonic Muscles)9
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Lecture 7: Smooth Muscle34
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Lecture 8: Muscle Diversity42
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Lecture 10-11: Locomotion81
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Midterm Review Slides204
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Lecture 9.1 and 9.2: Muscle Energy Metabolism84
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Lecture 10.1: Metabolic Scaling24
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Lecture 10.2: Paper 3 – Brand et al., 2003) Proton Conductance and Fatty Acyl Composition of Liver Mitochondria Correlates with Body Mass in Birds7
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Lecture 12.1: Thermal Biology and Metabolic Rate59
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Lecture 12.2: Paper 4 – Prioritization of Skeletal Muscle Growth for Emergence from Hibernation12
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Lecture 13.1: Dormancy and Muscle Atrophy32
