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- biol 370 > Lecture 4: EC Coupling (Striated Muscle) > Flashcards

Lecture 4: EC Coupling (Striated Muscle) Flashcards

1
Q

Which muscles does the somatic nervous system affect?

A

somatic nervous system → motor neurons → skeletal muscles

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2
Q

Which muscles does the autonomic nervous system affect?

A

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

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3
Q

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

A

excitation:

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

relaxation:

  • sarcolemma repolarizes and cytoplasmic [Ca2+] returns to resting levels
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4
Q
  1. Excitation

Are most vertebrate skeletal muscles neurogenic or myogenic?

A

most are neurogenic (stimulated by neurons)

  • stimulated by ACh from a motor neuron
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5
Q
  1. Excitation

What are twitch muscles innervated by?

A

each cell is innervated by one neuron

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6
Q
  1. Excitation

What are tonic muscles innervated by?

A

each cell is innervated by multiple neurons

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7
Q
  1. Excitation

What happens when motor neurons in vertebrates are stimulated?

A
  • motor neurons release ACh from synpatic vesicles
  • ACh diffuses across the neuromuscular synapse
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8
Q
  1. Excitation

What is the motor endplate?

A

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
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9
Q
  1. Excitation

What does excitation require?

A

requires depolarization of the sarcolemma

  • one open channel depolarizes the sarcolemma by approximately 0.3 mV
  • sarcolemma resting membrane potential is around -70 mV
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10
Q
  1. Excitation

What is depolarization due to?

A

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

  • voltage-gated Ca2+ channels open, allowing influx of Ca2+
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11
Q
  1. Excitation

What is repolarization due to?

A

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

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12
Q
  1. Excitation

Are the time courses of APs always the same?

A

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

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13
Q
  1. Excitation

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

A
  • multiple innervations – tonic muscles
  • invaginations of the sarcolemma – t-tubules
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14
Q
  1. Excitation

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

A

sarcolemmal invaginations

  • enhance AP penetration
  • more developed in larger, fast-twitch muscles
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15
Q
  1. Excitation

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

A

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)
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16
Q
  1. Excitation

What are terminal cisternae?

A

enlargements of the SR that increase Ca2+ storage

  • closely associated with t-tubules in many striated muscles
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17
Q
  1. Coupling

How does intracellular Ca2+ signaling occur?

A
  • 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
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18
Q
  1. Coupling

What are the transporters for Ca2+ signaling?

A

extracellular:

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

intracellular:

  • ryanodine receptor (RyR)
  • Ca2+ ATPase (SERCA)
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19
Q
  1. Coupling

What are dihydropyridine receptors (DHPR)?

A

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

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20
Q
  1. Coupling

What are ryanodine receptors (RyR)?

A

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

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21
Q
  1. Coupling

What is Ca2+ ATPase (SERCA)?

A

pumps Ca2+ from cytoplasm into SR

22
Q
  1. Coupling

How does depolarization-induced Ca2+ release occur?

A
  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
  1. Ca2+ exits SR through RyR, greatly increasing cytoplasmic [Ca2+], stimulating contraction
  2. Ca2+ ATPase and NaCaX pump Ca2+ out of the cell, and SERCA pumps Ca2+ into the SR, decreasing cytoplasmic [Ca2+] and allowing relaxation
23
Q
  1. Coupling

How does contraction occur?

A
  • 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
24
Q
  1. Coupling

What happens when there is low [Ca2+]?

A
  • 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
25
Q
  1. Coupling

What happens when there is high [Ca2+]?

A
  • 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
26
Q

Relaxation

How does relaxation occur?

A
  • 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
27
Q

Relaxation

What occurs?

A
  • 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)
28
Q

Relaxation

What is parvalbumin?

A

cytosolic Ca2+ buffer

29
Q

What is the latent period?

A

time between AP and start of contraction

  • reflects time for EC-coupling
30
Q

What is the contraction phase?

A

cytosolic Ca2+ is increasing as release > uptake

31
Q

What is the relaxation phase?

A

cytosolic Ca2+ is decreasing as reuptake > release

32
Q

Summation of Twitches

What occurs at lower frequencies of stimulation?

A

muscle fully relaxes between each stimulation

33
Q

Summation of Twitches

What occurs at higher frequencies of stimulation?

A

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
34
Q

What are the 3 types of muscle contractions?

A
  • shortening contractions
  • isometric contractions
  • lengthening contractions
35
Q

What are shortening contractions?

A

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

36
Q

What are isometric contractions?

A

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

37
Q

What are lengthening contractions?

A

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

38
Q

What is force (F)?

A

results in movement or stress in a system

  • measured in newtons (N)
  • for muscles, force = tension
39
Q

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

A

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

40
Q

What is work (W)?

A

unit of energy

  • measured in joules or calories
  • W = F x distance
41
Q

What is power (P)?

A

ate of doing work

  • P = W / time
  • P = F x velocity
  • can be altered by either changing force or velocity
42
Q

What is mechanical efficiency?

A

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
43
Q

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

A
  • cross-sectional area
  • concentration of Ca2+ in the cytoplasm
  • contraction velocity (rate of shortening)
  • sarcomere length (force-length relationship)
44
Q

How does cross-sectional area affect force production?

A

more area → more force

45
Q

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

A

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

46
Q

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

A

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
47
Q

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

A

~25%

48
Q

What are the two factors that muscle efficiency?

A
  • velocity of contraction
  • myosin isoforms
49
Q

Different Myosin Isoforms Affect Function

A
  • many different genes for myosin II
  • different muscle cells express different combinations of myosin II genes, producing thick filaments with different properties
50
Q

What are the different myosin isoforms?

A
  • 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

- biol 370 (15 decks)

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