Muscle 1 Flashcards
What are myofibrils?
Fibrils containing filaments e.g. actin and myosin
Describe myofiber
A cell, endomysium, multinucleate
What is epimysium ?
This surrounds muscle
What is perimysium?
Surrounds fascicles, form septa
What is the function of connective tissue in muscle?
Conveys muscle force to tendons
What makes up the thick filaments of muscle?
Myosin-molecular motor
Myosin movement is actin-dependent in striated muscles
What are the parts of muscle thick filaments?
- head portion
- tail portion
- neck domain (s2)
Describe the head portion of thick muscle filament
Head portion of myosin
- 2 globular heads(cross-bridges)
- Binds actin and hydrolyzes ATP
- ATPase activity Ca2+ dependent
Describe the tail portion of thick muscle filament
Tail portion of myosin
2 heavy chains form double helix structure or “tail”
Describe the Neck domain of thick muscle filaments
Neck domain (S2) of myosin
- Connects head and tail
- Lever arm rotates during head movement
- 4 light chains- modulate myosin activity
What are the components of thin filament?
- Actin
- Tropomyosin
- Troponin
Describe actin thin filament in muscle
Globular actin polymerized into double-stranded helical filamentous actin (F-Actin). Contains myosin binding sites
Describe tropomyosin of thin filament
Filamentous protein blocks myosin-binding sites on actin
Describe troponin of thin filament of muscle
Consists of 3 globular proteins
I) troponin T(T-tropomyosin): Attaches troponin complex to tropomyosin
II) troponin (I=inhibition): positions tropomyosin over myosin binding site on actin
III) Troponin C (C=Ca2+): Ca2+ binds calcium. Results movement of tropomyosin. Important for initiation of contraction
Summarize events of excitation contraction coupling
Neurotransmitters released diffuses across the synaptic cleft and attaches to ACh receptors on the sacrolemma
- Net entry of Na+ initiates an action potential which is propagated along the sacrolemma and down the T tubules
- Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca2+ release from terminal cisternae of SR into cytosol
- Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed
- Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sacramer; release of energy by ATP hydrolysis powers the cycling process
- Removal of Ca2+ by active transport into the SR after the action potential ends
- Tropomyosin blockage restored, blocking myosin binding sites on actin; contraction ends and muscle fiber relaxes
How is endplate potential converted to action potential?
- Net entry of Na+ through voltage gated Na+ channels initiates AP
- voltage gated action potential generated
- AP propagates across muscle surface (sacrolemma)-positive feedback, no change in amplitude
- Migrates down the transverse tubules
- (T-tubules= invagination of sacrolemma )
What are transverse tubules?
- Na+ channel propagated depolarization travels along T-tubule deep inside large, long cell
- T-tubule in close proximity to Sarcoplasmic reticulum
Continuous with cell surface, spread throughout entire cell
Why is myosin (thick filament) a molecular motor?
Allows movement
What are the two myosin binding sites?
Actin and ATP binding sites
What is the cause of the end plate potential?
Caused by influx of sodium in post synaptic membrane
Differentiate ligand and voltage gated channel
Ligand needs a neurotransmitter
Voltage gated- needs action potential
End plate potential is a ….
Graded potential, because the amplitude diminishes as it goes on
Explain the functioning of the t-tubule
- Muscle action potential travels down the T-tubule
- Action potential is SENSED by Dihydropurine(DHP) receptor/L-typevvoltage gated calcium channel
- This activates Ryanodine receptor and it causes the opening of this receptor
- The opening of this receptor opens and allows for the flow of calcium from the sarcoplasm into the cytosolic space
- Increase cytosolic Ca2+ results in muscle contraction
Why is DHP is a sensor and not a channel in skeletal muscles?
In cardiac muscles there are extracellular sources for calcium while in skeletal muscles, the only sources for calcium are the SR
Therefore in cardiac muscle, it is a channel and a sensor in skeletal muscle
What is the role of calcium?
Resting muscle
- Intracellular calcium very low (<10^-9M or nM)
- Majority of calcium stored in sarcoplasmic reticulum
- Ca2+ bound to SR proteins e.g. calsequestrin
Contracting muscle
- Muscle depolarization—> Ca2+ release from SR
- SR ONLY source of Ca2+ for contraction (skel m.)
- Intracellular calcium increased (>10^-5 or high uM)
Relaxation
-Calcium actively pumped from the cytoplasm back into SR by SERCA pumps on SR membrane (Sarco/endoplasmic Ca2+ ATPase )(in the absence of energy we can’t pump calcium back)
-calsequestrin reduces free Ca2+ within the SR, reducing Ca2+ concentration gradient across SR, which assists SERCA pumping
Summarize the role of calcium for muscle contraction
-Skeletal muscle contraction
Relaxed state: low calcium <10^-9 M Ca2+, interaction between actin and myosin low, blocked by tropomyosin
Contracted state: High Ca2+ > 10^-5 M Ca2+
Ca2+ saturates troponin C
This leads to tropomyosin inhibition, All myosin binding sites exposed
“All or none” contraction
-binds to troponin which causes
Give the steps of the cross bridge cycle
- At rest, the interaction between Myosin and Actin is blocked allosterically by tropomyosin
- Ca2+ binds to troponin-C; uncovering the myosin-binding sites on the actin filaments. The myosin head binds to actin
- The release of ADP and P changes the conformation of the myosin head from 90 degrees to 45 degrees, stretching the myosin head
- The recoil of the myosin head creates the power stroke
Following this movement (which results in a relative filament displacement of around 10nm). The actin-myosin binding is still strong, and the cross bridge can not detach. At this point in the cycle, the state of actin-myosin binding is termed a Rigor cross bridge
- The detachment of the Rigor Crossbridge is possible when a new ATP molecule binds to the myosin head and is subsequently hydrolyzed
- Energy from ATP hydrolysis resets the myosin head from a 45 degree confirmation back to its original 90 degree conformation, thereby returning the myosin and actin positions to their original resting state
What is active tension?
The force generated by the cross ridge cycling is called active tension
Explain the sliding filament hypothesis/ Hypothesis of Huxley
-Sliding action results from repeated “attachment and detachment” of the heads of the myosin molecules and neighboring actin filaments
- Sarcomere shortens and becomes thicker, but the myofilaments remain the same length
- A band remains constant(thick filament )
- H and I band both decreases in size
- Z lines are drawn closer to the ends of the A bands
Changes in the amount of overlap between thick and thin filaments allow for contraction and relaxation of muscle fibers
Essentially actin moves over myosin while myosin stays still
Explain the length tension relationship
1,2 Actin filament overlap-The force that can be exerted by myosin tugging on actin is compromised, and active tension is less. At this point actin is overlapping itself, blocking myosin. Force of contraction is 0
3,4 optimal length- The number of myosin-binding sites on actin and the number of myosin heads available for contraction are at maximum. This length produces maximum active tension. Relative force- 1
5,6 reduces actin-myosin interaction - decreased filament overlap occurs with increasing stretch. Thus fewer actin-myosin interaction is available for cross bridges (implies bone fracture)
Note: most skeletal muscles are within optimal length due to muscle attachment due to bone
In muscle PHYSIOLOGY, the word contracting refers to…
Generation of tension/force with or without shortening of the stimulated muscle
What is twitch?
A single action potential bringing about a brief contraction followed by relaxation
This is called a muscle twitch
What is a isometric contract?
Contract but no movement, generate tension
How can an isometric twitch be measured?
- Muscle fixed/ clamped at specific length
- Single stimulation- external shock
- Force of contraction measured (myosin/actin cross bridges)
- Can stretch muscle and repeat- to measure force generated at different lengths
What is an isotonic contraction?
Contraction that results in movement
Describe each of the 4 phases of isotonic contraction
Phase 1 isometric contraction- when the muscle is stimulated, it will begin to develop force without shortening.
Phase 2 isotonic contraction - After sufficient force has been generated, the muscle will begin to shorten and lift the load.
Phase 3 isotonic relaxation- As Ca2+ levels decrease, relaxation begins, the muscle lengthens at constant force because it is still supporting the load.
Phase 4 isometric relaxation- return to its original length, as the remaining force in the muscle declines
