Lecture 4: EC Coupling (Striated Muscle) Flashcards
Which muscles does the somatic nervous system affect?
somatic nervous system → motor neurons → skeletal muscles
Which muscles does the autonomic nervous system affect?
autonomic nervous system → sympathetic and parasympathetic nervous system → smooth, cardiac muscle
What are the general steps in EC-coupling in a typical skeletal muscle?
excitation:
- excitation: action potential depolarizes sarcolemma (cell membrane)
- coupling: depolarization linked to Ca2+ release from sarcoplasmic reticulum
- coupling: Ca2+ binds to troponin, shifts configuration of tropomyosin, revealing myosin binding sites on actin
- contraction: cross-bridge cycling and sarcomere shortening
relaxation:
- sarcolemma repolarizes and cytoplasmic [Ca2+] returns to resting levels
- Excitation
Are most vertebrate skeletal muscles neurogenic or myogenic?
most are neurogenic (stimulated by neurons)
- stimulated by ACh from a motor neuron
- Excitation
What are twitch muscles innervated by?
each cell is innervated by one neuron
- Excitation
What are tonic muscles innervated by?
each cell is innervated by multiple neurons
- Excitation
What happens when motor neurons in vertebrates are stimulated?
- motor neurons release ACh from synpatic vesicles
- ACh diffuses across the neuromuscular synapse
- Excitation
What is the motor endplate?
specialized postsynaptic region of a muscle cell immediately across from the synaptic cleft from the presynaptic axon terminal
- is extensively folded and has high density of nicotinic ACh
- Excitation
What does excitation require?
requires depolarization of the sarcolemma
- one open channel depolarizes the sarcolemma by approximately 0.3 mV
- sarcolemma resting membrane potential is around -70 mV
- Excitation
What is depolarization due to?
due to opening of Na+ channels (followed by Ca2+ channels in cardiac muscle)
- voltage-gated Ca2+ channels open, allowing influx of Ca2+
- Excitation
What is repolarization due to?
due to opening of K+ channels (followed by Cl- channels in skeletal muscles)
- Excitation
Are the time courses of APs always the same?
no – time course of AP in muscle cell varies in different muscle types
- Excitation
How do muscles ensure uniform depolarization of the sarcolemma for contraction?
- multiple innervations – tonic muscles
- invaginations of the sarcolemma – t-tubules
- Excitation
What are transverse tubules (t-tubules)? Where are they found? What do they do?
sarcolemmal invaginations
- enhance AP penetration
- more developed in larger, fast-twitch muscles
- Excitation
What are sarcoplasmic reticulums (SR)? Where are they found? What do they do?
extensions of the sarcolemma that extend into the cell
- common in muscles that have rapid response to stimulation
- stores Ca2+ – Ca is bound to calsequestrin (protein that binds calcium)
- Excitation
What are terminal cisternae?
enlargements of the SR that increase Ca2+ storage
- closely associated with t-tubules in many striated muscles
- Coupling
How does intracellular Ca2+ signaling occur?
- extracellular [Ca2+]: 2-3 mM
- intracellular [Ca2+]: (in SR) 50-250 μM
- during contraction, cytoplasmic [Ca2+] can increase 100x over resting values (up to 20 μM)
- cellular Ca2+ increases to initiate contraction
- Coupling
What are the transporters for Ca2+ signaling?
extracellular:
- dihydropyridine receptor (DHPR)
- Ca2+ ATPase
- Na+/Ca2+ exchanger (NaCaX)
intracellular:
- ryanodine receptor (RyR)
- Ca2+ ATPase (SERCA)
- Coupling
What are dihydropyridine receptors (DHPR)?
voltage-gated Ca2+ channels located in the sarcolemma, where Ca2+ enters the cell when opened
- Coupling
What are ryanodine receptors (RyR)?
Ca2+ channels located in the membrane of the sarcoplasmic reticulum (SR), where Ca2+ leaves the SR when opened
- Coupling
What is Ca2+ ATPase (SERCA)?
pumps Ca2+ from cytoplasm into SR
- Coupling
How does depolarization-induced Ca2+ release occur?
- depolarization of the sarcolemma during AP causes DHPR to open, allowing Ca2+ to enter the cell
- NOTE: in some striated muscles (particularly those that contract relatively slowly), influx of Ca2+ from extracellular space through DHPR will raise the cytoplasmic [Ca2+] sufficiently for muscle contraction
- in other striated muscles, Ca2+ must also be released from SR in order to trigger muscle contraction
- in striated muscles that contract rapidly, SR stores large amounts of Ca2+
- DHPR and RyR are physically linked – structural change in DHPR opens RyR
- Ca2+ exits SR through RyR, greatly increasing cytoplasmic [Ca2+], stimulating contraction
- Ca2+ ATPase and NaCaX pump Ca2+ out of the cell, and SERCA pumps Ca2+ into the SR, decreasing cytoplasmic [Ca2+] and allowing relaxation
- Coupling
How does contraction occur?
- increase in [Ca2+] results
- Ca2+ binds to TnC
- strengthened TnC-TnI interaction
- weakened TnI to actin interaction
- troponin-tropomyosin complex move into actin groove
- actin-myosin cross-bridge cycling
- Coupling
What happens when there is low [Ca2+]?
- during relaxation, [Ca2+] in cytoplasm is low (< 200 nM)
- TnC regulatory sites cannot bind Ca2+
- troponin-tropomyosin complex blocks the myosin binding sites on the thin filament
- Coupling
What happens when there is high [Ca2+]?
- excitation of the muscle increases cytoplasmic [Ca2+]
- TnC regulatory sites bind Ca2+, which causes a structural reorganization of the troponin-tropomyosin complex such that it rolls into the groove of the thin filament and exposes the myosin binding sites
Relaxation
How does relaxation occur?
- Ca2+ binds parvalbumin
- Ca2+ pumped across sarcolemma and into SR
- Ca2+ released by TnC
- weakened TnC-TnI interaction
- strengthened TnI-actin interaction
- troponin-tropomyosin return to inhibitory position
Relaxation
What occurs?
- membrane repolarization
- re-establish Ca2+ gradients
- return Ca2+ to extracellular space – Ca2+ ATPase and Na+/Ca2+ exchanger (NaCaX) work in reverse
- return Ca2+ to SR – Ca2+ ATPase (SERCA)
Relaxation
What is parvalbumin?
cytosolic Ca2+ buffer
What is the latent period?
time between AP and start of contraction
- reflects time for EC-coupling
What is the contraction phase?
cytosolic Ca2+ is increasing as release > uptake
What is the relaxation phase?
cytosolic Ca2+ is decreasing as reuptake > release
Summation of Twitches
What occurs at lower frequencies of stimulation?
muscle fully relaxes between each stimulation
Summation of Twitches
What occurs at higher frequencies of stimulation?
muscle does not have time to relax between stimulations
- second AP is generated before the first contraction is complete, increasing the magnitude of the contraction/force – contractile summation
- sufficiently high frequencies of stimulation will induce a sustained contraction at maximum force – tetanus
What are the 3 types of muscle contractions?
- shortening contractions
- isometric contractions
- lengthening contractions
What are shortening contractions?
activated muscle shortens in length during contraction (ie. bicep curl)
What are isometric contractions?
activated muscle remains at a fixed length (ie. postural muscles)
What are lengthening contractions?
activated muscle increases in length (ie. some leg muscles during descent)
What is force (F)?
results in movement or stress in a system
- measured in newtons (N)
- for muscles, force = tension
How much force can each myosin head in a thick filament produce?
each myosin head in can produce around 5 pN of force during a cross-bridge cycle
What is work (W)?
unit of energy
- measured in joules or calories
- W = F x distance
What is power (P)?
ate of doing work
- P = W / time
- P = F x velocity
- can be altered by either changing force or velocity
What is mechanical efficiency?
ratio of mechanical work produced by muscle and metabolic energy required to produce that work
- OR ratio of power output to metabolic energy needed to generate power (measure of how effective a muscle system is at converting metabolic energy into power)
- no units
What are the factors that affect force production? (4)
- cross-sectional area
- concentration of Ca2+ in the cytoplasm
- contraction velocity (rate of shortening)
- sarcomere length (force-length relationship)
How does cross-sectional area affect force production?
more area → more force
How does the concentration of Ca2+ in the cytoplasm affect force production?
more Ca2+ → more force, but there seems to be a threshold
How does contraction velocity (rate of shortening) affect force production?
slower → more force
- P = 0 when is force is so high that muscle cannot contract, therefore has velocity = 0
- muscles have an optimal velocity of contraction that can yield maximal power
- P = 0 when velocity of a muscle is so high that it cannot generate force via A-M interactions
What is the muscle efficiency of a typical muscle that is working ‘optimally’?
~25%
What are the two factors that muscle efficiency?
- velocity of contraction
- myosin isoforms
Different Myosin Isoforms Affect Function
- many different genes for myosin II
- different muscle cells express different combinations of myosin II genes, producing thick filaments with different properties
What are the different myosin isoforms?
- alpha: fast cardiac isoform expressed in cardiac muscle, in species with faster heart rates, or in response to activity
- beta: slow cardiac/slow oxidative isoform expressed in cardiac muscle of species with slower heart rates, type I (slow oxidative) skeletal fibres
- IIa: found in fast oxidative-glycolytic fibres – ATPase rates intermediate between I and IIx/d
- IIx/d: found in fast glycolytic fibres – ATPase rates intermediate between IIa and IIb
- IIb: found in fast glycolytic fibres – fastest ATPase rates
