Which of the following layers contain capillary network, myosatellite cells, and nerve fibers?
B. Endomysium (endo=inner)
Layer that surrounds the entire muscle
Epimysium
Layer that surrounds muscle fascicles (bundles of muscle fibers)
Perimysium
Layer that surrounds individual muscle fiber
Endomysium
What connects muscle to bone?
Tendons
Organization of skeletal muscle
At the end of each muscle, collagen fibers of the epimysium, perimysium & endomysium come together to form a bundle (tendon) or sheet (aponeurosis) that attaches to bone
Formation of skeletal muscle fibers
Myoblasts (muscle germ cells) fuse to form skeletal muscle fibers
Myoblasts that do NOT fuse with developing muscle fibers reamin & are called myosatellite cells
Myosatellite cells
Myoblasts that do not fuse with developing muscle fibers remain
Help with muscle repair... Can enlarge & fuse with damaged muscle fibers
Found in endomysium
Structure of a skeletal muscle fiber
Muscle fiber membrane
Sarcolemma
Structure of a skeletal muscle fiber
Cytoplasm of muscle fiber
Sarcoplasm
Structure of a skeletal muscle fiber
T (transverse) tubules
Narrow tubes, continuous wiht sarcolemma, extend into sarcoplasm at right angles to cell surface
Action potentials travel down these tubules to initiate muscle contraction
Structure of a skeletal muscle fiber
Myofibrils
Bundles of protein filaments (myofilaments) attached at each end of sarcolemma
Actively shorten during contraction
Contain thick & thin filaments
Mitochondria surround these myofibrils (energy)
Structure of a skeletal muscle fiber
Sarcoplasmic reticulum (SR)
Similar to smooth ER of other cells
Expands near T tubules to form chambers called terminal cisternae
Structure of a skeletal muscle fiber
Triad
Pair of terminal cisternae & a T tubule
Myofibrils structure
Made up of thick and thin filaments, titin
Organized into repeating sarcomeres (functional units)
Sarcomeres Structure
A bands (dArk) -length of thick filaments
I bands (LIght)- contains thin filaments but NOT thick
Sarcomere structure
A Band
M line: connection point of thick filaments
H band: light region on either side of M line
* contains ONLY thick filaments
Zone of overlap: region of overlap between thick & thin filaments
Sarcomere Structure
I Band
Z lines: boundaries between adjacent sarcomeres
responsible for the banded (striated) appearance of muscle
Titin: elastic protein that attaches thick filaments to Z lines
Connection point of thick filaments
M line (in A band)
Light region on either side of M line
H Band (in A band)
Elastic protein that attaches thick filaments to Z lines
Titin
Responsible for the banded (striated) appearance of muscle
Z lines ( in I BAND)
Region of overlap between thick & thin filaments
Zone of overlap
Light region on either side of M line
H band ( contains only thick filaments)
Connection point of thick filaments
M line (in A band)
Sarcomere structure
Thin & Thick filaments are organized 3-dimensionally too
(ex. in the zone of overlap, 3 thick filaments surround each thin filament & 6 thin filaments sound each thick filament)
What makes up the thin filaments?
Actin, Nebulin, Tropomyosin, Troponin
Thin Filaments
Actin
F (filamentous) actin: composed to 2 rows of G (globular) actin molecules
Each G actin molecule contains an active site that can bind to myosin
Thin Filaments
Nebulin
Runs through middle of F actin strand, holds it together
Thin Filaments
Tropomyosin
Double stranded protein that covers 7 active sites on G actin molecules
Each is bound to one troponin molecule
Double stranded protein that covers 7 active sites on G actin molecules
Tropomyosin
Thin Filaments
Troponin
Contains 3 subunits, when bound to calcium changes conformation & moves tropomysosin off of active sites
1. Troponin C: binds Calcium (calcium levels are very low in resting state & only increase to initiate contraction)
2. Troponin T: binds to Tropomyosin
3. Troponin I: binds to actin
Which of the following binds to actin?
A. Troponin I
Double stranded protein that covers 7 active sites on G actin molecules
Tropomyosin
Composed of 2 rows of G actin molecules
F actin
Runs through middle of F actin strand, holds it together
Nebulin
Thick Filaments
Myosin
Contain about 300 myosin molecules
Contains head & tail region ( head interacts with actin... formation of cross bridges) (tails are all pointed toward M lines)
What happens to these filaments during contraction ?
1. Thin filaments slide toward center of each sarcomere, alongside thick filaments (sliding filament theory)
2. H band & I bands get smaller
3. Zones of overlap get larger
4. Z lines move closer together
5. Width of A band remains constant.
Big Picture of Contraction
If sarcomeres shorten during contraction then:
Myofibrils will shorten
Entire muscle will shorten
What controls Skeletal Muscle Activity?
Nervous systerm (but remember it is VOLUNTARY)
Control of Skeletal Muscle Activity:
Where nerve & skeletal muscle meet & communicate
Neuromuscular junction (NMJ)
Control of skeletal muscle activity:
Synaptic terminal
Nerve axon braches & ends here
Contains vesicles filled with acetylcholine (ACh)
Control of skeletal muscle activity:
Synaptic Cleft
Narrow space between synaptic terminal & sarcolemma
Contains enzyme acetylcholinesterase (AChE) which breaks down ACh
Control of skeletal muscle activity
Motor end plate
Sarcolemmal surface containing ACh receptors
Which of the following is the sarcolemmal surface containing ACh receptors?
D. Motor end plate
Narrow space between synaptic terminal & sarcolemma
Synaptic Cleft
Neural Stimulation of a muscle fiber:
Step 1: Arrival of an action potential at the synaptic terminal
Step 2: Release of acetylcholine: Vesicles in the synaptic terminal fuse with the neuronal membran and dump their contents into the synaptic cleft
Step 3: ACh binding at the motor end plate: the bind of ACh to the receptors increase the membrane permeability to sodium ions. Sodium ions then rush into the cell
Step 4: Appearance of an action potential in the sarcolemma: An action potential spreads across the surface of the sarcolemma. While this occurs, AChE breaks down the ACh
Step 5. Return to initial state: If another action potential arrives at the NMJ, the cycle begins again at step 1
Excitation- Contraction coupling
E-C Coupling
Link between generation of action potential in sarcolemma & start of muscle contraction
Occurs at triads
Action potential travels down T tubules, triggers Ca2+ release from terminal cisternae of the SR
Exposure of active sites
Action potential triggers realse of Ca2+ from SR
Ca2+ binds to troponin C
Troponin moves tropomyosin, exposing active sites
Exposure of active sites leads to cross-bridge formation
Contraction Cycle
1. Release of Ca2+ that binds to troponin, which pulls tropomysin off , ACTIVE SITE EXPOSURE
2. Myosin head attaches to acting: CROSS-BRIDGE FORMATION
3. Stored energy is release (ADP+P), myosin head pivots toward the M line= power stroke: PIVOTING OF MYOSIN HEAD
4. When a new ATP molecule binds to the myosin head, the link between the active site on actin & the myosin head is broken: CROSS BRIDGE DETACHMENT
5. Myosin reactivation occurs when ATP is broken down into ADP+P, myosin head recocks: MYOSIN REACTIVATION
Contaction Cycle
1. ACTIVE SITE EXPOSURE
2. CROSS-BRIDGE FORMATION
3. PIVOTING OF MYOSIN HEAD
4. CROSS BRIDGE DETACHMENT
5. MYOSIN REACTIVATION
***if calcium ions are still present & there is sufficient ATP, this cycle will continue to be repeated (several times per second) until calcium gets taken up***
Shortening during a contraction
A) During contraction, if neither end of myofibril is held in place, both ends move towards middle
B) In intact skeletal muscle, one end of muscle is usually fixed (the origin) while the other end moves (the insertion)- THE FIXED END MOVES THE FREE END
Muscle Contraction Summary (simplified version)
1. ACh released, binding to receptors
2. Action Potential reaches T tubule
3. Sarcoplasmic Reticulum releases Ca2+
4. Active site exposure, cross-bridge formation
5. Contraction begins
Muscle Relaxation Summary (simplified version) aka steps that END a contraction
6. ACh removed by ACHe
7. Sarcoplasmic reticulum recaptures Ca2+
8. Active sites covered, no cross-bridge interaction
9. Contraction ends
10. Relaxation occurs, passive return to resting length
Muscle Contraction Summary (extended version)
1. At the neuromuscular junction (NMJ), ACh released by the synaptic terminal binds to receptors on the sarcolemma
2. The resulting ∆ in the transmembrane potential of the muscle fiber leads to the production of an action potential that spreads across the entire surface of the muscle fiber and along the T tubules
3. The SR releases stored Ca2+, increasing calcium concentration of the sarcoplasm in & around the sarcomeres
4. Ca2+ bind to troponin, producing a ∆ in the orientation of the troponin-tropomyosin complex that exposes active sites on the thin (actin) filaments. Cross bridges form when myosin heads bind to active sites on F actin.
5. The contraction begins as repeated cycles of cross-bridge binding, pivoting, and detachment occur, powered by the hydrolysis of ATP. These events produce filament sliding and the muscle fiber shortens.
Muscle Relaxation Summary (extended version)
6. Action potential generation ceases as ACh is broken down by acetylcholinesterase (AChE)
7. The SR reabsorbs Ca2+ & the concentration of Ca2+ in the sarcoplasm declines
8. When Ca2+concentrations approach normal resting levels, the troponin -tropomyosin complex returns to its normal position. This ∆ re-covers the active sites & prevents further cross-bridge interaction.
9. Without cross-bridge interactions, further sliding cannot take place, & the contraction ends
10. Muscle relaxation occurs & the muscle returns passively to its resting length
Death: no oxygen & nutrients, so muscle runs out of ATP, calcium leaks into sarcoplasm; without ATP cross-bridges can't be broken= RIGOR MORTIS: sustained contraction, starts 15-25 hours after death & ending 72 hours or more later
Muscle Tension
Amount of tension produced by a muscle fiber depends on the number of cross-bridges, but can vary depending on:
1. Fiber's resting length at time of stimulation (relates to degree of overlap between thin & thick filaments)
Optimal length= most efficient = most tension produced
Overstretch= cross-bridge interaction is reduced or absent
Decreased resting lengths= thin filaments extend across center of sarcomere= decrease of tension
2. Frequency of stimulation
Muscle tension
Frequency of stimulation
A single stimulation produces a single contraction , or twitch
Repeated stimulation produces a sustained contraction
Muscle tension
Treppe ("stairs")
When a second stimulus arrives immediately after relaxation phase has ended, the next contraction will develop slightly higher tension
--due to increased Ca2+ in sarcoplasm (because Ca2+ doesnt have enough time to all be pumped back into SR)
Muscle Tension
Wave Summation
When a second stimulus arrives before relaxation phase has ended, the second contraction will have increased tension
Muscle Tension
Incomplete Tetanus
Increased stimulation frequency, muscle almost never allowed to relax completely, 4 times the tension produced compared to wave summation
Muscle tension
Complete Tetanus
Higher frequency stimulation completely eleminates relaxation phase, causes continuous contraction.
Tension production by skeletal muscles
Tension produced by whole skeletal muscles depends on:
The tension produced by the stimulated muscle fibers
The total number of muscle fibers stimulated
Motor unit:
all the muscle fibers (usually around 100) controlled by a single motor neuron
Tension production by skeletal muscle
The total number os muscle fibers stimulated
Recruitment: increasing the number of active motor units to increase muscular tension produced
-Max tension produced when all motor units in muscle are in state of complete tetanus
-Typically during sustained contraction motor units are activated on a rotating basis- asynchronous motor unit summation (TO PREVENT FATIGUE)
Muscle Tone
Resting Tension: some motor units are active, but not enough to produce movement
Stabilizes postitions of bones and joints
Prevents uncontrolled, sudden ∆s in position
Related to basal metabolic rate... the more muscle tone the higher the basal metabolic rate
Some motor units are active, but not enough to produce movement
Variable severity depending on the type of mutation
Ex: Duchenne's muscular dystrophy (DMD)- mutation in gene that codes for dystrophin (protein that attaches thin filaments to anchoring proteins on sarcolemma) - X-linked inheritance pattern, so more males affected
Myotonic dystrophy- alteration in gene that codes for a myosin kinase
Malignant Hyperthermia
Symptoms cause by inherited defect in receptor that allows calcium to be released from SR & initiate muscle contraction
Hereditary impairment to sequester calcium, leads to prolonged released of calcium (body can't keep up)
Symptoms include: rapid rise in body temperature greater than 105 degrees F
Muscle rigidity & stiffness
Dark brown urine (due to rhabdomyolysis)
Increased heart rate
Acidosis (low blood pH)
Usually triggered by general anesthetic
Patients given DANTROLENE (muscle relaxant that dissociates excitation-contraction coupling)
Symptoms cause by inherited defect in receptor that allows calcium to be released from SR & initiate muscle contraction
Malignant Hyperthermia
Patients that have _________________are given DANTROLENE
Malignant Hyperthermia
Drugs that Relax Skeletal Muscle
Spasmolytics
Acts to decrease muscle spasms & increase muscle tone
(ex. Diazepam, Baclofen)
Which of the following is a spasmolytic drug?
D. Diazepam
Drugs that relax skeletal muscle
Neuromuscular blocking drugs
Nondepolarizing: Antangonist at ACh receptor, prevents ACh from binding, prevent depolarization
Used as adjuncts during general anesthesia to facilitate tracheal intubation & optimize surgical conditions
Can be reversed by cholinesterase inhibitors (ex. Tubocurarine, Cistatracurium)
Depolarizing: acts as a depolaring agonist at ACh receptor: phase 1 it binds to receptor & causes depolarization, not metabolized effectively at synapse, so membranes remain depolarized & unresponsive to subsequent impulses (depolarizing block); in phase 2 acts as if channel is prolonged closed state (desensitized)
Can be reversed by cholinesterase inhibitors, but only during phase 2 (ex. Succinylcholine-only one approved in US)
