3. Skeletal Muscle Physiology Flashcards
Requirements for Skeletal Muscle Contraction
• Activation:
– ____ at neuromuscular junction.
• Excitation-contraction coupling:
– Generation and propagation of an ____ along the
sarcolemma, which causes…
• Final trigger: a rise in intracellular ____.
neural stimulation
action potential
Ca2+
Neuromuscular Transmission and Excitation-Contraction Coupling
- Muscle innervation by myelinated nerve fibers from motor neurons in the spinal cord.
- ____: The parent axon and all the muscle fibers that it innervates.
- Neuromuscular junction: specialized structure of nerve terminals associated with target muscle.
- Nerves transmit a membrane depolarization signal (action potential; to be studied in BS-IV) to the muscles.
- Axon terminal releases ____ into the synaptic cleft in response to the action potential.
motor unit
acetylcholine (ACh)
Neuromuscular Transmission and Excitation-Contraction Coupling: 1. Resting Membrane Potential
• Nervous system:
– Controls muscle contractions through
action potentials.
• Resting membrane potentials:
– Membrane voltage difference across membranes (____) caused by ____ differences on the two sides of a membrane.
– Normal (resting) potential is negative:
• Muscle cells: ____ mV.
Every cell at the level of its membrane has an electrical charge, and this electrical charge is distributed differently extracellularly and intracellularly > polarized; when you have a resting cell > slight difference in the amount of charge on both sides > the inner side is slightly more ____ than the outer side (polarization)
Due to differential ____ and ____
polarization
ion concentration
-70/-90
negative
transports
permeabilities
Neuromuscular Transmission and Excitation-Contraction Coupling: 2. Action Potential
• Action potential:
– Change in membrane potential from a negative resting potential to a ____ potential (depolarization), and back to the negative resting potential (____).
– Used to transmit signals (e.g. nerve impulse).
– Amplitude (strength) ____ with distance from initial site
AP > change in membrane potential at level at any PM > goes from negative to positive (on the inside, this is depolarization, now ____ mV from -70 mV) > due to the influx of ____ ions
The AP transmits itself ____ > once passes a point > repolarization via the trafficking of ____ ions
positive
repolarization
constant
+25
Na+
sequentially
K+
Neuromuscular Transmission and Excitation-Contraction Coupling: 3. Neurotransmitter Release
- ACh stored in neuronal synaptic vesicles.
- AP travels down the nerve fiber (1).
- Depolarization opens ____ channels (2).
- Influx of Ca+2 (3): synaptic vesicles fuse with the membrane (4) and release ACh into the synaptic cleft (5).
voltage-gated Ca2+
Excitation-Contraction Coupling: End Plate Potential
- Local depolarization (end plate potential):
– Resting muscle membrane potential: -70/-90 mV.
– Nicotinic ACh receptors at the ____:
• ____ ion channels:
–Binding of ACh induces a conformational
change in the channel to open to the ____ movement of positive ions (____»_space; K+ > Ca2+).
– Net result: + charge enters cell, so voltage inside cell rises (becomes less negative), i.e. depolarization (____) to ~ ____ mV.
Creation of local depolarization at the level of the end plate (due to the traffic of Na+ ions) > end plate potential (not an ____ at this point, but will create one)
sarcolemma ACh-gated inward Na+ end plate potential ~0 action potential
Excitation-Contraction Coupling: End Plate Potential
2. Generation and propagation of the AP:
– End plate potential propagates along the ____.
– Change in voltage opens ____ Na+ channels: Na+ influx → plasma membrane depolarization.
– If ____ is reached, an AP is generated: local depolarization spreads.
sarcolemma
voltage-gated
treshold
Excitation-Contraction Coupling: End Plate Potential
3. Repolarization:
– ____ channels close and ____ channels open.
– K+ ____ through the open K+ channels.
– Loss of + charge returns membrane to its
negative resting potential.
Na+
voltage-gated K+
exits
Excitation-Contraction Coupling: 1. Role of T Tubules
- ____ is required for myofilament contraction.
- Ca2+ must be liberated from the SR.
- Therefore, current must penetrate deeply into the muscle fiber.
- But… skeletal muscle fibers are too large to produce current flow deep inside the cells.
- Solution: APs are transmitted along the ____ which extend to the proximity of the SR.
- APs in the T tubules cause Ca2+ release in the vicinity of the myofibrils, causing contraction.
- The overall process is called ____.
Ca2+
T tubules
excitation-contraction coupling
Excitation-Contraction Coupling: 2. Release of Ca2+
• Voltage change (action potential) in the T tubules activates the ____.
• Activation of DHP receptors opens Ca2+ release channels (____) in the SR.
• Channels open for a few ____, releasing Ca2+ into the sarcoplasm.
• High [Ca2+] in the vicinity of the myofibrils causes their contraction.
DHPR are activated by a change in polarity (inner side of membrane is polarized) > ____ to the Ca-release channels in the SR > once DHPR are activated, it’ll force these channels open > resulting in an expulsion of Ca2+ ions from the SR released in vicinity of the myofibrils
dihdropyridine (DHP) receptors
ryanodine receptor channels
milliseconds
mechanically linked
Excitation-Contraction Coupling: 3. Re-uptake of Ca2+
• Repolarization:
• Causes ____ receptors to close the Ca2+ release channels in
the SR.
• Ca2+ is pumped back into the SR by a ____ (____: Sarco/Endoplasmic RetiCulum ATPase).
• Inside the SR, the protein ____ serves to concentrate stored Ca2+ .
• Low [Ca2+] in the vicinity of the myofibrils stops their contraction.
DHP
Ca2+ pump
SERCA
calsequestrin
Contraction of Skeletal Muscle: The Calcium Switch
• Absence of Ca2+ (____ M):
–____ binds Ca2+ → shift in position of tropomyosin: ____ within the groove between the two actin chains.
–Myosin-binding sites on actin are exposed: myosin binds tightly to actin (cross-bridge).
–Cross-bridge cycling occurs, over and over, as long as ____ is high and ____ is available.
–When nervous stimulation ceases, Ca2+ is pumped back into SR and contraction ends.
Since Ca2+ control in skeletal muscle is at the thin filaments: ____
(In smooth muscle > ____-linked Ca regulation)
10-9
tropomyosin/troponin complex
10-5 troponin C deeper [Ca2+] ATP actin-linked regulation myosin
Contraction of Skeletal Muscle: Cross-bridge Cycle
- Binding of myosin to actin:
• Myosin head is bound to ____→ high-energy conformation and high affinity for actin.
• ATP has been hydrolyzed but energy can not be released until myosin head can interact with actin: requires activation of ____ by Ca2+
ADP + Pi
tropomyosin
Contraction of Skeletal Muscle: Cross-bridge Cycle
- Powerstroke:
• Release of ____ → ____ in the myosin head: “power stroke” that moves actin and myosin filaments relative to each other.
Pi
conformational change
Contraction of Skeletal Muscle: Cross-bridge Cycle
- Rigor:
• Release of ____ → conformational change in myosin to a ____.
• Myosin remains ____ to actin subunit.
• Myosin in a conformation with high affinity for ____ (lower affinity for ____).
ADP low-energy form bound ATP actin
Contraction of Skeletal Muscle: Cross-bridge Cycle
- Unbinding of myosin and actin:
• Binding of ATP to the myosin head: conformational change → unbinding from ____.
ATP binds to the ____ domain of the myosin head following release of binding to actin
actin
ATPase
Contraction of Skeletal Muscle: Cross-bridge Cycle
- Cocking of the myosin head:
• ATP hydrolysis by the ATPase activity at the myosin head.
• Released energy forces the myosin head into its ____
from where the cycle can repeat itself (“____” model).
Hydrolyzes ATP into ADP and Pi > ____ the myosin (preparing it to “shoot” and act upon actin) and will restart the cycle if calcium is present
high-energy conformation
walk-along
cocks
Every time we go around one cross-bridge cycle we burn ____ per myosin head, and we move the actin filament to the left
1 ATP
Neuromuscular Transmission and Excitation-Contraction Coupling: Summary
- Arrival of an action potential at the neuromuscular junction and induction of ____ release.
- Activation by ACh of ____ channels and depolarization of the sarcolemma (action potential).
- Transmission of the action potential: ____ depolarization of the sarcolemma, including T tubule system.
- Activation of the ____ receptors.
- Ca2+ release from the SR (____ channels).
- Binding of Ca2+ to ____ at the thin (actin) myofilament.
- Troponin/tropomyosin conformational unmasking of myosin-binding sites on actin.
- Start of the cross-bridge cycle.
ACh nicotinic ACh-gated Na+ sequential DHP receptors ryanodine troponin C
Energetics of Skeletal Muscle Contraction
First immediate source of energy > ____ stores of ATP (relatively low); if contraction lasts longer than ____ seconds, these stores are depleted
The cell then switches to the use of ____ (ATP carrier); after these are depleted (____ seconds) > uses ____ from use of imported glucose from liver or intracellular stores of glycogen, or as a more stable source of energy the cell will use the ____
intracellular 1-2 creatine phosphate 8 glycolysis Krebs/TCA/ox. phos.
Energetics of Skeletal Muscle Contraction
• Efficiency of muscle contraction: ____ (at the ATP level).
• Energy consumption:
– ____ (contraction).
– ____ (SERCA; relaxation).
– ____ (ion balance restoration during repolarization).
• Muscle cells require modest levels of ATP when at rest, and substantial amounts of ATP during intense contraction.
• Energy sources (in order of use):
– Hydrolysis of ATP stores:
• 1-2 seconds.
– Hydrolysis of phosphocreatine.
– Glycogenolysis and anaerobic glycolysis.
– Oxidative metabolism.
40-45%
myosin ATPase
Ca2+-ATPase
Na+/K+-ATPase
Energetics of Skeletal Muscle Contraction
• Hydrolysis of ____:
– 5-8 seconds.
– Shuttles phosphate groups from mitochondria to myofibrils.
Following hydrolysis of ATP stores
Phosphocreatine is the result of phosphorylation of ____ with ATP > now it is a carrier of ATP > migrate to myofibrils to myosin, and there is creatine phosphokinase (located within the ____ of the sarcomere, where the reverse reaction takes place)
Before contraction, cell has free ATP in storage and as phosphocreatine (eventually also gets depleted after 8 seconds, and must be regenerated in mitochondria or glycolytic pathway)
phosphocreatine
creatine
H line
Energetics of Skeletal Muscle Contraction
• Glycogenolysis and anaerobic glycolysis: – O2 supply to muscle is limited - \_\_\_\_ exercise. – Anaerobic glycolysis to \_\_\_\_ and fermentation to \_\_\_\_: low energy efficiency. – Accumulation of lactate: muscle \_\_\_\_. – Time scale: \_\_\_\_.
Glycolytic pathway is an ____ method of producing ATP
Has two advantages: very ____ pathway to produce energy, and quickly mobilizes the stores of carbs already present in muscle as glycogen
intense pyruvate lactate soreness minutes inefficient
quick
Energetics of Skeletal Muscle Contraction
• Oxidative metabolism: – Sustained, long-term contraction (e.g. aerobic exercises). – Requires adequate \_\_\_\_ supply: • High rate of \_\_\_\_ (breathing). • High heart \_\_\_\_. • Vasodilation.
– For 2-4 h: 50% of energy from ____.
– >4 h: ____ stores.
– Following exercise, respiration is still increased
(____) because oxidative phosphorylation continues to:
• Replenish ____ and ____ stores.
• Convert ____ to pyruvate to glucose in the
liver.
O2
lung ventilation
contraction rate
carbohydrates lipid oxygen deficit phenomenon creatine-P glycogen lactate
