WEEK 6 (Basis of Skeletal muscle contraction) Flashcards
What are the different movements that contraction of muscles allow?
- Purposeful movement of the whole body or parts of the body
- Manipulation of external objects (e.g driving a car)
- Propulsion of contents through hollow internal organs
- Emptying the contents of certain organs to the external environment
What can muscles be categorised into?
- STRIATED or UNSTRIATED (depending on whether alternating dark and light bands or striations (stripes) can be seen under light microscope)
- VOLUNTARY or INVOLUNTARY
(depending if innervated by SOMATIC NERVOUS SYSTEM (voluntary control) or AUTONOMIC NERVOUS SYSTEM (involuntary control))
Describe the Skeletal Muscle
CLASSIFICATION: Striated & voluntary muscle
DESCRIPTION: Bundles of long, thick, cylindrical, striated, contractile, multinucleate cells that extend the length of the muscle
TYPICAL LOCATION: Attached to bones of the skeleton
FUNCTION: Movement of the body in relation to the external environment
Describe the Cardiac Muscle
CLASSIFICATION: Striated & Involuntary muscle
DESCRIPTION: Interlinked network of short, slender, cylindrical, striated, branched, contractile cells connected cell to cell by intercalated discs
LOCATION: Wall of heart
FUNCTION: Pumping of blood out of the heart
Describe the Smooth Muscle
CLASSIFICATION: Unstriated & Involuntary muscle
DESCRIPTION: Loose network of short, slender, spindle-shaped, unstriated, contractile cells that are arranged in sheets
TYPICAL LOCATION: Walls of hollow organs and tubes (e.g stomach and blood vessels)
FUNCTION: movement of contents with hollow organs
Describe the Smooth Muscle
CLASSIFICATION: Unstriated & Involuntary muscle
DESCRIPTION: Loose network of short, slender, spindle-shaped, unstriated, contractile cells that are arranged in sheets
TYPICAL LOCATION: Walls of hollow organs and tubes (e.g stomach and blood vessels)
FUNCTION: movement of contents with hollow organs
What is a muscle fibre?
A single skeletal muscle cell that is relatively large, elongated and cylinder shaped
Describe the properties of Skeletal muscle
- consists of a number of muscle fibers lying parallel to one another and bundled together by connective tissue
- fibers usually extend the entire length of muscle
- ## abundance of mitochondria due to high energy demands
Describe the Embryonic development of skeletal muscle fibres
During embryonic development, the huge skeletal muscle fibres are formed by the fusion of many smaller cells called MYOBLASTS; this explains the presence of multiple nuclei dispersed just beneath the plasma membrane in a single muscle cell
What are Myofibrils?
- A skeletal muscle fibre contains numerous MYOFIBRILS
- Each myofibril consists of a regular arrangement of highly organised cytoskeletal microfilaments (THICK & THIN filaments)
- THICK filaments are made of MYOSIN
- THIN filaments are made of ACTIN
What are the levels of organisation in a skeletal muscle?
1) MYOSIN & ACTIN (protein molecules)
2) THICK & THIN FILAMENTS (cytoskeletal elements)
3) MYOFIBRIL (a specialised intracellular structure)
4) MUSCLE FIBRE (a cell)
5) WHOLE MUSCLE (organ)
What can be seen when viewed with an electron microscope?
A myofibril that display alternating dark bands (A bands) and light bands (I bands)
The bands of all the myofi- brils lined up parallel to one another collectively produce the striated appearance of a skeletal muscle fiber visible under a light microscope.
What is responsible for the A and I bands?
Alternate stacked sets of thick and thin filaments that slightly overlap one another
Describe the key components of the A band
- made up of a stacked set of thick filaments along with the portions of the thin filaments that overlap on both ends of the thick filaments
- the thick filaments lie only within the A band and extend its entire width
- the H ZONE is the lighter area within the middle of the A band where the thin filaments do not reach
- upporting proteins that hold the thick filaments together vertically within each stack can be seen as the M LINE, which extends vertically down the middle of the A band within the center of the H zone.
Describe the key components of the I band
- consists of the remaining portion of the thin filaments that do not project into the A band
- In the middle of each I BAND is a dense, vertical Z LINE
- SARCOMERE is the area between the two Z lines which is the functional unit of skeletal muscle
What is the Sarcomere?
Sarcomere is the area between the two Z lines which is the smallest component of a muscle fibre that can contract
What is the Z line?
a flat, cytoskeletal disc that connects the thin filaments of two adjoining sarcomeres
What does each sarcomere consist of?
One whole A band and half of each of the two I bands located on either side
Describe what happens during growth
- a muscle increases in length by adding new sarcomeres on the ends of the myofibrils, not by increasing the size of each sarcomere
- single strands of a giant, highly elastic protein known as TITIN extend in both directions from the M line along the length of the thick filament to the Z lines at opposite ends of the sarcomere
What is Titin and what are its functions?
Titin is the largest protein in the body made up of nearly 30,000 amino acids
- SERVING AS SCAFFOLDING - helps stabilise the position of thick filaments in relation to thin filaments contributing to sarcomere stability
- ACTING AS AN ELASTIC SPRING - helps a muscle stretched by an external force passively recoil to its resting length when the stretching force is removed accounting for the PARALLEL-ELASTIC component of muscle
- PARTICIPATING IN SIGNAL TRANSDUCTION
What are the properties of Cross bridges?
- With an electron microscope, can be seen extending from each thick filament towards the surrounding thin filaments in the areas where the thick and thin filaments overlap
- Three dimensionally, the thin filaments are arranged hexagonally around the thick filaments
- Cross bridges project from each thick filament in all six directions towards the six surrounding thin filaments
- Each thin filament is surrounded by THREE thick filaments
Describe Myosin
- a protein consisting of TWO IDENTICAL SUBUNITS shaped like a golf club with ends that are intertwined around each other
- Myosin can bend along the tail and at the “neck” or junction of the tail with each head
- The two halves of each thick filament are mirror images made up of myosin molecules lying lengthwise in a regular, staggered array, with their tails oriented towards the centre of the filament and their globular heads protruding outward at regular intervals
- Heads form the cross bridges between the thick and thin filaments
What are the two sites of cross bridges that are crucial to the contractile process?
- an actin-binding site
- a myosin ATPase (ATP-splitting) site
Describe Actin
- spherical
- each actin molecule has a binding site for attaching with a myosin cross bridge
- in a relaxed muscle fibre, contraction doesn’t take place since actin cannot bind with cross bridges because of the way TROPOMYOSIN and TROPONIN are positioned within the thin filament
Thin filaments consist of which proteins?
- actin
- tropomyosin
- troponin
Describe the thin filament’s backbone
Formed by actin molecules joined into two strands and twisted together. Each actin molecule has a binding site for attaching with a myosin cross bridge. Binding of myosin and actin at the cross bridges leads to contraction of the muscle fibre.
Describe Tropomyosin
Molecules that are threadlike proteins that lie end to end alongside the groove of the actin spiral. In this position (relaxed), it covers the actin sites that bind with cross bridges, blocking the interaction that leads to muscle contraction.
Describe Troponin
A protein complex made of three polypeptide units: one binds to tropomyosin, one binds to actin, one with Ca2+
Describe how Troponin works in muscle control
When troponin is not bound to Ca2+, this protein stabilises tropomyosin in its blocking position over actin’s cross-bridge sites.
When Ca2+ binds to troponin, the shape of this protein is changed that tropomyosin slips away from its blocking position. With tropomyosin out of the way, actin and myosin can bind and interact at the cross bridges, resulting in muscle contraction.
Why are Tropomyosin and Troponin often called “regulatory proteins”?
Because of their role in covering (preventing contraction) or exposing (permitting contraction) the binding sites for cross-bridge interaction between actin and myosin
Describe what happens when a muscle is relaxed
1) No excitation
2) No cross-bridge binding because cross-bridge binding site on actin is physically covered by troponin-tropomyosin complex
3) Muscle fiber is relaxed
Describe what happens when a muscle is excited
1) Muscle fiber is excited and Ca2+ is released
2) Released Ca2+ binds with troponin, pulling troponin-tropomyosin complex aside to expose cross-bridge binding site
3) Cross-bridge binding occurs
4) Binding of actin and myosin cross bridge triggers power stroke that pulls thin filament inward during contraction
What causes muscle contraction?
Cross-bridge interaction between actin and myosin brings about muscle contraction by means of a sliding filament mechanism
Describe the Sliding filament mechanism
1) The thin filaments on each side of a sarcomere slide inward over the stationary thick filaments towards the A band’s centre during contraction
2) As they slide inwards, the thin filaments pull the Z lines to which they are attached closer together, so the sarcomere shortens. Since all sarcomeres throughout the muscle fibres length shorten simultaneously, the entire fiber shortens.
3) H ZONE becomes smaller as the thin filaments approach each other when they slide more deeply inward, the I BAND narrows as the thin filaments overlap the thick filaments during their inward slide.
4) Thin and thick filaments do not change length & width of A BAND remains unchanged
Why does the width of the A band remain unchanged during contraction?
The width is determined by the length of the thick filaments and the thick filaments do not change length during the shortening process
If contraction is not caused by the shortening of the filaments, what is it caused by?
Contraction is accomplished by the thin filaments from the opposite sides of each sarcomere sliding closer together between the thick filaments
Describe what happens during a ‘Power Stroke’
1) When the binding site on an actin molecule is exposed, the myosin molecule tilts at the hinge point on the tail, elevating the myosin head to facilitate the binding of this cross bridge to the nearest actin molecule
2) The myosin head tilts 45 degrees inward. Bending at this neck hinge point creates a “stroking” motion that pulls the thin filament towards the centre of the sarcomere
(a single power stroke pulls the thin filament inward only a SMALL PERCENTAGE of the total shortening distance so repeated cycles of cross-bridge binding and bending complete the shortening)
3) Link between the myosin cross bridge and actin molecule breaks. Cross bridge detaches at the end of power stroke and returns to original confirmation
4) Cross bridge binds to the actin molecule behind its previous actin partner, tilts inward again to pull the thin filament in farther, detaches and the cycle repeats.
The two Myosin heads of each Myosin molecule act ________________ with only one head attaching to actin at a given time
Independently
What is Asynchronous cycling of the cross bridges and why is it important?
At any time during contraction, part of the cross bridges are attached to the thin filaments and are stroking while others are returning to their original confirmation in preparation for binding with another actin molecule. Some are “holding on” to the thin filaments, whereas others “let go” to bind with new actin.
If it weren’t for the asynchronous cycling of the cross bridges, the thin filaments would slip back towards their resting position between strokes.
Define Excitation-contraction coupling
The series of events linking muscle excitation to muscle contraction
What is the plasma membrane in muscle called?
Sarcolemma
Skeletal muscles are stimulation to contract by the release of which neurotransmitter?
ACETYLCHOLINE at neuromuscular junctions between motor neuron terminal buttons and muscle fibers
Describe the importance of the Transverse tubules
TRANSVERSE TUBULES (T TUBULES) run perpendicularly from the surface of the muscle cell membrane into the central portions of the muscle fiber & are found when the surface membrane of each junction of an A BAND and I BAND dips into the muscle fibre.
Since the T tubule membrane is continuous with the Sarcolemma, an action potential on the surface membrane spreads down into the T tubule, rapidly transmitting the surface electrical activity into the interior of the fiber. The presence of a local action potential in the T tubules leads to permeability changes in a separate membranous network within the muscle fiber (SARCOPLASMIC RETICULUM).
What is the Sarcoplasmic reticulum?
A modified endoplasmic reticulum that consists of a fine network of interconnected membrane-enclosed compartments surrounding each myofibril like a mesh sleeve
Describe the Sarcoplasmic reticulum
- encircles myofibril throughout its length but isn’t continuous
- separate segments are wrapped around each A band and each I band
- end of each segment expand to form LATERAL SACS/TERMINAL CISTERNAE
- lateral sacs store Ca2+
- spread of an action potential down a T tubules triggers release of Ca2+ from the SR into the cytosol
How is a change in T tubule potential linked with the release of Ca2+ from the lateral sacs?
- T tubule membrane proteins (DIHYDROPYRIDINE RECEPTORS) are voltage sensors; local depolarisation of the T tubules activates dihydropyridine receptors which trigger the opening of FOOT PROTEINS in adjacent lateral sacs
- FOOT PROTEINS span the gap between the T tubule & the lateral sac and serve as Ca2+ RELEASE CHANNELS (RYANODINE RECEPTORS)
- When FOOT PROTEINS are opened in the presence of a local action potential in the adjacent T tubule, Ca2+is released into the cytosol from the lateral sacs
- By slightly repositioning the troponin and tropomyosin molecules, this released Ca2+ exposes the binding sites on the actin molecules so that they can link with the myosin cross bridges at their complementary binding sites
What are the two sites on a myosin cross bridge?
An actin-binding site & an ATPase site
Describe the stages of ATP-powered cross bridge cycling
1) ATP is split by myosin ATPase; ADP and Pi remain tightly bound to myosin and the generated energy is stored within the cross bridge to produce a HIGH ENERGY FORM of myosin
2) Ca2+ is released on excitation which removes inhibitory influence from actin, enabling it to bind with the cross bridge
3) Power stroke of cross bridge is triggered on contact between myosin and actin; Pi is released during and ADP is released after power stroke
4) Linkage between actin and myosin is reduced as a fresh molecule of ATP binds to myosin cross bridge; cross bridge assumes original confirmation and ATP is hydrolysed
What happens when there is no excitation?
No Ca2+ is released, actin and myosin is prevented from binding, there is no cross-bridge cycle and muscle fiber remains at rest.
How long does Rigor Mortis take place?
It begins 3-4 hours after death and completes in about 12 hours
Describe what happens in Rigor Mortis
- Cytosolic conc. of Ca2+ starts to rise since INACTIVE MUSCLE MEMBRANE cannot keep out extracellular Ca2+ and Ca2+ leaks out of the lateral sacs
- Ca2+ moves troponin and tropomyosin aside, letting actin bind with the myosin cross bridges, which were already charged with ATP before death
- Dead cells cannot produce more ATP so actin and myosin cannot detach thus stay linked by IMMOBILISED CROSS BRIDGES, leaving dead muscles stiff
Describe how Relaxation occurs
Contractile process is turned off and relaxation occurs when Ca2+ is returned to the LATERAL SACS. The SARCOPLASMIC/ENDOPLASMIC RETICULUM Ca2+ ATPASE (SERCA) PUMP actively transports Ca2+ from the cytosol and concentrates it in the lateral sacs.
What is the ‘Latent Period’?
The time delay of a few milliseconds between stimulation and onset of contraction
