Lecture 4: EC Coupling (Striated Muscle)

Question 1

Which muscles does the somatic nervous system affect?

Answer 1

somatic nervous system → motor neurons → skeletal muscles

Question 2

Which muscles does the autonomic nervous system affect?

Answer 2

autonomic nervous system → sympathetic and parasympathetic nervous system → smooth, cardiac muscle

Question 3

What are the general steps in EC-coupling in a typical skeletal muscle?

Answer 3

excitation:

• 1. excitation: action potential depolarizes sarcolemma (cell membrane)
• 2. coupling: depolarization linked to Ca2+ release from sarcoplasmic reticulum
• 3. coupling: Ca2+ binds to troponin, shifts configuration of tropomyosin, revealing myosin binding sites on actin
• 4. contraction: cross-bridge cycling and sarcomere shortening

relaxation:

• sarcolemma repolarizes and cytoplasmic [Ca2+] returns to resting levels

Question 4

1. Excitation

Are most vertebrate skeletal muscles neurogenic or myogenic?

Answer 4

most are neurogenic (stimulated by neurons)

• stimulated by ACh from a motor neuron

Question 5

1. Excitation

What are twitch muscles innervated by?

Answer 5

each cell is innervated by one neuron

Question 6

1. Excitation

What are tonic muscles innervated by?

Answer 6

each cell is innervated by multiple neurons

Question 7

1. Excitation

What happens when motor neurons in vertebrates are stimulated?

Answer 7

• motor neurons release ACh from synpatic vesicles
• ACh diffuses across the neuromuscular synapse

Question 8

1. Excitation

What is the motor endplate?

Answer 8

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

Question 9

1. Excitation

What does excitation require?

Answer 9

requires depolarization of the sarcolemma

• one open channel depolarizes the sarcolemma by approximately 0.3 mV
• sarcolemma resting membrane potential is around -70 mV

Question 10

1. Excitation

What is depolarization due to?

Answer 10

due to opening of Na+ channels (followed by Ca2+ channels in cardiac muscle)

• voltage-gated Ca2+ channels open, allowing influx of Ca2+

Question 11

1. Excitation

What is repolarization due to?

Answer 11

due to opening of K+ channels (followed by Cl- channels in skeletal muscles)

Question 12

1. Excitation

Are the time courses of APs always the same?

Answer 12

no – time course of AP in muscle cell varies in different muscle types

Question 13

1. Excitation

How do muscles ensure uniform depolarization of the sarcolemma for contraction?

Answer 13

• multiple innervations – tonic muscles
• invaginations of the sarcolemma – t-tubules

Question 14

1. Excitation

What are transverse tubules (t-tubules)? Where are they found? What do they do?

Answer 14

sarcolemmal invaginations

• enhance AP penetration
• more developed in larger, fast-twitch muscles

Question 15

1. Excitation

What are sarcoplasmic reticulums (SR)? Where are they found? What do they do?

Answer 15

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)

Question 16

1. Excitation

What are terminal cisternae?

Answer 16

enlargements of the SR that increase Ca2+ storage

• closely associated with t-tubules in many striated muscles

Question 17

2. Coupling

How does intracellular Ca2+ signaling occur?

Answer 17

• 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

Question 18

2. Coupling

What are the transporters for Ca2+ signaling?

Answer 18

extracellular:

• dihydropyridine receptor (DHPR)
• Ca2+ ATPase
• Na+/Ca2+ exchanger (NaCaX)

intracellular:

• ryanodine receptor (RyR)
• Ca2+ ATPase (SERCA)

Question 19

2. Coupling

What are dihydropyridine receptors (DHPR)?

Answer 19

voltage-gated Ca2+ channels located in the sarcolemma, where Ca2+ enters the cell when opened

Question 20

2. Coupling

What are ryanodine receptors (RyR)?

Answer 20

Ca2+ channels located in the membrane of the sarcoplasmic reticulum (SR), where Ca2+ leaves the SR when opened

Question 21

2. Coupling

What is Ca2+ ATPase (SERCA)?

Answer 21

pumps Ca2+ from cytoplasm into SR

Question 22

2. Coupling

How does depolarization-induced Ca2+ release occur?

Answer 22

1. 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

2. Ca2+ exits SR through RyR, greatly increasing cytoplasmic [Ca2+], stimulating contraction
3. Ca2+ ATPase and NaCaX pump Ca2+ out of the cell, and SERCA pumps Ca2+ into the SR, decreasing cytoplasmic [Ca2+] and allowing relaxation

Question 23

3. Coupling

How does contraction occur?

Answer 23

• 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

Question 24

3. Coupling

What happens when there is low [Ca2+]?

Answer 24

• 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

Question 25

3. Coupling What happens when there is high [Ca2+]?

Answer 25

- 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

Question 26

Relaxation How does relaxation occur?

Answer 26

- 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

Question 27

Relaxation What occurs?

Answer 27

- 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)

Question 28

Relaxation What is parvalbumin?

Answer 28

cytosolic Ca2+ buffer

Question 29

What is the latent period?

Answer 29

time between AP and start of contraction - reflects time for EC-coupling

Question 30

What is the contraction phase?

Answer 30

cytosolic Ca2+ is increasing as release > uptake

Question 31

What is the relaxation phase?

Answer 31

cytosolic Ca2+ is decreasing as reuptake > release

Question 32

Summation of Twitches What occurs at lower frequencies of stimulation?

Answer 32

muscle fully relaxes between each stimulation

Question 33

Summation of Twitches What occurs at higher frequencies of stimulation?

Answer 33

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

Question 34

What are the 3 types of muscle contractions?

Answer 34

- shortening contractions - isometric contractions - lengthening contractions

Question 35

What are shortening contractions?

Answer 35

activated muscle shortens in length during contraction (ie. bicep curl)

Question 36

What are isometric contractions?

Answer 36

activated muscle remains at a fixed length (ie. postural muscles)

Question 37

What are lengthening contractions?

Answer 37

activated muscle increases in length (ie. some leg muscles during descent)

Question 38

What is force (F)?

Answer 38

results in movement or stress in a system - measured in newtons (N) - for muscles, force = tension

Question 39

How much force can each myosin head in a thick filament produce?

Answer 39

each myosin head in can produce around 5 pN of force during a cross-bridge cycle

Question 40

What is work (W)?

Answer 40

unit of energy - measured in joules or calories - W = F x distance

Question 41

What is power (P)?

Answer 41

ate of doing work - P = W / time - P = F x velocity - can be altered by either changing force or velocity

Question 42

What is mechanical efficiency?

Answer 42

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

Question 43

What are the factors that affect force production? (4)

Answer 43

- cross-sectional area - concentration of Ca2+ in the cytoplasm - contraction velocity (rate of shortening) - sarcomere length (force-length relationship)

Question 44

How does cross-sectional area affect force production?

Answer 44

more area → more force

Question 45

How does the concentration of Ca2+ in the cytoplasm affect force production?

Answer 45

more Ca2+ → more force, but there seems to be a threshold

Question 46

How does contraction velocity (rate of shortening) affect force production?

Answer 46

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

Question 47

What is the muscle efficiency of a typical muscle that is working 'optimally'?

Answer 47

~25%

Question 48

What are the two factors that muscle efficiency?

Answer 48

- velocity of contraction - myosin isoforms

Question 49

Different Myosin Isoforms Affect Function

Answer 49

- many different genes for myosin II - different muscle cells express different combinations of myosin II genes, producing thick filaments with different properties

Question 50

What are the different myosin isoforms?

Answer 50

- 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