1. Muscle Contraction and Motor Unit
Chapter 9 Motor System - 1
Muscle Contraction and Motor Unit

2. Content
Skeletal Muscle Contraction
Motor Unit

3. Reference – Text Book P71– 82 P482-483
UNIT XI The Nervous System: C. Motor and Integrative Neurophysiology P

4. Section I Skeletal Muscle Contraction
Signal Transmission Through Neuromuscular Junction
Molecular Mechanism of Muscle Contraction
Factors that Affect the Efficiency of Muscle Contraction

5. Part I Signal Transmission Through the Neuromuscular Junction

6. Skeletal Muscle Innervation

7. Illustration of the Neuromuscular Junction (NMJ)

8. New Ion Channel Players
Voltage-gated Ca2+ channel
in presynaptic nerve terminal
mediates neurotransmitter release
Nicotinic Acetylcholine Receptor Channel
in muscle neuromuscular junction (postsynaptic membrane, or end plate)
mediates electrical transmission from nerve to muscle

9. Neuromuscular Transmission
Myelin
Axon
Axon Terminal
Skeletal Muscle

10. Neuromuscular Transmission: Step by Step - - Nerve action
Depolarization
of terminal
opens Ca channels
Nerve action
potential invades
axon terminal - + + -
+ +
Look
here

11. Na+ Na+ Na+ Na+ K+ Na+ K+ Na+ K+ K+ Na+ Na+ K+ Na+ Na+ Na+ K+ K+ Na+
Binding of ACh opens
channel pore that is
permeable to Na+ and K+.
ACh binds to its
receptor on the
postsynaptic membrane
ACh is released and
diffuses across
synaptic cleft.
Ca2+ induces fusion of
vesicles with nerve
terminal membrane.
ACh
ACh
ACh
Nerve
terminal
Ca2+
Ca2+
Na+
Na+
Na+
Na+ K+
Na+ K+
Na+ K+ K+
ACh
Na+
Na+
Na+ K+
Outside
Muscle membrane
Na+
Na+
Inside K+ K+
Na+ K+ K+ K+ K+ K+
Na+ K+
Na+

12. End Plate Potential (EPP，终板电位)
The movement of Na+ and K+
depolarizes muscle membrane
potential (EPP)
VNa
EPP
Muscle Membrane
Voltage (mV)
Threshold
Presynaptic
terminal
-90 mV VK
Time (msec)
Presynaptic AP
Outside
Muscle membrane
Inside
Voltage-gated
Na Channels
ACh Receptor Channels
Inward Rectifier
K Channels

13. Meanwhile ... ACh ACh ACh Choline resynthesized ACh is hydrolyzed by
into ACh and repackaged
into vesicle
Choline is taken up
into nerve terminal
ACh is hydrolyzed by
AChE into Choline
and acetate
ACh unbinds from
its receptor
so the channel closes
Nerve
terminal
Choline
ACh
Acetate
ACh
Outside
Muscle membrane
Inside

14. Structural Reality

15. Neuromuscular Transmission
Properties of neuromuscular junction
1:1 transmission:
An unidirectional process
Has a time delay. 20nm/0.5-1ms
easily affect by drugs and some factors
The NMJ is a site of considerable clinical importance

16. Clinical Chemistry Related compounds are Ach is the natural
useful in the neuroscience
research
Suberyldicholine is a
synthetic neuromuscular
agonist.
Ach is the natural
agonist at the
neuromuscular
junction.
Carbachol and related
compounds are used
clinically for GI disorders,
glaucoma, salivary
gland malfunction, etc.
Tubocurarine and other,
related compounds
are used to paralyze
muscles during surgery.
Tubocurarine competes
with ACh for binding
to receptor- but does
not open the pore.
So tubocurarine is a
neuromuscular
blocking agent.
Carbachol is a
synthetic agonist
not hydrolyzed by
acetylcholinesterase.
Tubocurarine is the
primary paralytic
ingredient in curare.

17. Anticholinesterase Agents
Anticholinesterase (anti-ChE 胆碱酯酶抑制剂) agents inhibit acetylcholinesterase （乙酰胆碱酯酶）
prolong excitation at the NMJ

18. Anticholinesterase Agents
1. Normal:
ACh Choline + Acetate
AChE
2. With anti - AchE:
ACh Choline + Acetate
anti - AChE

19. Uses of anti-ChE agents
Clinical applications (Neostigmine, 新斯的明, Physostigmine毒扁豆碱)
Insecticides (organophosphate 有机磷酸酯)
Nerve gas (e.g. Sarin 沙林，甲氟膦酸异丙酯。一种用作神经性毒气的化学剂))

20. VX NERVE AGENT

21. NMJ Diseases Myasthenia Gravis （重症肌无力）
Autoimmunity to ACh receptor
Fewer functional ACh receptors
Low “safety factor” for NM transmission
Lambert-Eaton syndrome（兰伯特-伊顿综合征 ，癌性肌无力综合征 ）
Autoimmunity directed against Ca2＋ channels
Reduced ACh release

22. Botulinum toxin antiserum (肉毒杆菌毒素抗血清）
The symptoms of Myasthenia
Gravis could be relieved by
Atropine
Botulinum toxin antiserum (肉毒杆菌毒素抗血清）
Curare
Halothane （氟烷）
Neostigmine

23. Prat II Molecular Mechanism of Muscle Contraction

24. Structure of Skeletal Muscle: Microstructure
Sarcolemma （肌管系统）
Transverse (T) tubule
Longitudinal tubule (Sarcoplasmic reticulum, SR 肌浆网)
Myofibrils （肌原纤维）
Actin 肌动蛋白 (thin filament)
Troponin （肌钙蛋白）
Tropomyosin （原肌球蛋白）
Myosin 肌球蛋白 (thick filament)

25. Within the Sarcoplasm Triad （三联管） Transverse tubules （横管）
Sarcoplasmic reticulum - Storage sites for calcium
Terminal cisternae - Storage sites for calcium

26. Sarcomeres bundle of alternating thick and thin filaments
join end to end to form myofibrils
Thousands per fiber, depending on length of muscle
Alternating thick and thin filaments create appearance of striations

28. Thick filament: Myosin (肌球蛋白，head and tail)
Thin filament: Actin 肌动蛋白, Tropomyosin 原肌球蛋白, Troponin (肌钙蛋白 calcium binding site)

29. What protein is the principle component
of skeletal muscle thick filaments?
actin
myosin
troponin
calmodulin
tropomyosin

30. Molecular Mechanism of Muscular Contraction
The sliding filament model 肌丝滑行
Muscle shortening is due to movement of the actin filament over the myosin filament
Reduces the distance between Z-lines

31. The Sliding Filament Model of Muscle Contraction

32. Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber

33. Energy for Muscle Contraction
ATP is required for muscle contraction
Myosin ATPase breaks down ATP as fiber contracts

34. Nerve Activation of Individual Muscle Cells (cont.)

35. Excitation/contraction coupling
Action potential along T-tubule causes release of calcium from cisternae of TRIAD
Cross-bridge cycle

36. Begin cycle with myosin already bound to actin

37. 1. Myosin heads form cross bridges
Myosin head is tightly bound to actin in rigor state
Nothing bound to nucleotide binding site

38. 2. ATP binds to myosin
Myosin changes conformation, releases actin

39. 3. ATP hydrolysis ATP is broken down into:
ADP + Pi (inorganic phosphate)
Both ADP and Pi remain bound to myosin

40. 4. Myosin head changes conformation
Myosin head rotates and binds to new actin molecule
Myosin is in high energy configuration

41. 5. Power stroke
Release of Pi from myosin releases head from high energy state
Head pushes on actin filament and causes sliding
Myosin head splits ATP and bends toward H zone. This is Power stroke.

42. 6. Release of ADP
Myosin head is again tightly bound to actin in rigor state
Ready to repeat cycle

43. A + M l ADP l Pi AlMlADPlPi A – M l ATP AlM THE CROSS-BRIDGE CYCLE
Relaxed state
Crossbridge energised
Crossbridge attachment
A + M l ADP l Pi
Ca2+ present
A – M l ATP
AlMlADPlPi
Crossbridge detachment
Tension develops
ADP + Pi
ATP
AlM
A, Actin; M, Myosin

44. Cross Bridge Cycle

45. Rigor mortis
Myosin cannot release actin until a new ATP molecule binds
Run out of ATP at death, cross-bridges never release

46. Rigor mortis is caused by
buildup of lactic acid
lack of Ca2
depletion of glycogen
lack of ATP.
deficient acetylcholine receptors.

47. Need steady supply of ATP!
Many contractile cycles occur asynchronously during a single muscle contraction
Need steady supply of ATP!

48. Regulation of Contraction
Tropomyosin blocks myosin binding in absence of Ca2+
Low intracellular Ca2+ when muscle is relaxed

49. Ca+2 binds to troponin during contraction
Troponin-Ca2+ pulls tropomyosin, unblocking myosin-binding sites
Myosin-actin cross-bridge cycle can now occur

50. How does Ca2+ get into cell?
Action potential releases intracellular Ca2+ from sarcoplasmic reticulum (SR)
SR is modified endoplasmic reticulum
Membrane contains Ca2+ pumps to actively transport Ca2+ into SR
Maintains high Ca2+ in SR, low Ca2+ in cytoplasm

51. Ca2+ Controls Contraction
Ca2+ Channels and Pumps
Release of Ca2+ from the SR triggers contraction
Reuptake of Ca2+ into SR relaxes muscle 19

52. Structures involved in EC coupling - Skeletal Muscle -
T-tubule
sarcolemma
out in
sarcoplasmic
reticulum
voltage sensor?
junction foot

53. Dihydropyridine （DHP, 双氢吡啶） Receptor
In t-tubules of heart and skeletal muscle
Nifedipine and other DHP-like molecules bind to the "DHP receptor" in t-tubules
In heart,
a voltage-gated Ca2+ channel
In skeletal muscle,
voltage-sensing protein
undergoes voltage-dependent conformational changes 20

54. Ryanodine (利阿诺定 ) Receptor
The "foot structure" in terminal cisternae of SR
Foot structure is a Ca2+ channel of unusual design
Conformation change or Ca2+ -channel activity of DHP receptor
gates the ryanodine receptor,
opening and closing Ca2+ channels
Many details are yet to be elucidated! 21

55. Skeletal muscle The AP: moves down the t-tubule
voltage change detected by DHP （双氢吡啶） receptors
DHP receptor is essentially a voltage-gated Ca channel
is communicated to the ryanodine receptor which opens to allow Ca out of SR
activates contraction
out in
voltage sensor
(DHP receptor)
junctional foot
(ryanodine receptor)
sarcoplasmic
reticulum
sarcolemma
T-tubule

56. Cardiac muscle The AP: moves down the t-tubule
voltage change detected by DHP receptors (Ca2+ channels) which opens to allow small amount of (trigger) Ca2+ into the fibre
Ca2+ binds to ryanodine receptors which open to release a large amount of (activator) Ca2+ (CACR)
Thus, calcium, not voltage, appears to trigger Ca2+ release in Cardiac muscle!
out in
voltage sensor
& Ca channel
(DHP receptor)
junctional foot
(ryanodine receptor)
sarcoplasmic
reticulum
sarcolemma
T-tubule

57. Comparison Skeletal Cardiac
The trigger for SR release appears to be calcium (Calcium Activated Calcium Release - CACR)
The t-tubule membrane has a Ca2+ channel (DHP receptor)
The ryanodine receptor is the SR Ca release channel
The ryanodine receptor is Ca- gated & Ca release is proportional to Ca2+ entry
Skeletal
The trigger for SR release appears to be voltage (Voltage Activated Calcium Release- VACR)
The t-tubule membrane has a voltage sensor (DHP receptor)
The ryanodine receptor is the SR Ca release channel
Ca2+ release is proportional to membrane voltage

58. Summary: Excitation-Contraction Coupling

59. The Ca2+ required for skeletal
muscle contraction
is released from the sarcoplasmic reticulum
enters the cell due to the opening of voltage regulated Ca2+ channels from the T tubules.
is actively transported into the cell.
is released from mitochondria.

60. What structures carry the action potentials into the interior of the
muscle to cause muscle contraction?
T tubules
terminal cisternae
DHP receptor
Ryanodine ceceptor

61. Part III Factors that Affect the Efficiency of Muscle Contraction

62. Tension 张力 and Load 负荷
The force exerted on an object by a contracting muscle is known as tension.
The force exerted on the muscle by an object (usually its weight) is termed load.
According to the time of effect exerted by the loads on the muscle contraction the load was divided into two forms, preload and afterload.

63. Preload 前负荷 Preload Initial length
load on the muscle before muscle contraction.
Determines the initial length of the muscle before contraction.
Initial length
the length of the muscle fiber before its contraction.
positively proportional to the preload.

64. The Effect of Sarcomere Length on Tension
The Length – Tension Curve
Concept of optimal length

65. Types of Contractions I
Twitch 单收缩: a brief mechanical contraction of a single fiber produced by a single action potential at low frequency stimulation is known as single twitch.
Tetanus 强直收缩: summation of twitches that occurs at high frequency stimulation

66. Effects of Repeated Stimulations
Figure 10.15

67. 1/sec
5/sec
10/sec
50/sec

68. Afterload 后负荷 Afterload
load on the muscle after the beginning of muscle contraction.
reverse force that oppose the contractile force caused by muscle contraction.
does not change the initial length of the muscle
prevent muscle from shortening

69. Types of Contractions (II)
Afterload is resistance
Isometric 等长
Length of muscle remains constant. Peak tension produced. Does not involve movement
Isotonic 等张
Length of muscle changes. Tension fairly constant. Involves movement at joints
Resistance and speed of contraction inversely related

70. Isotonic and Isometric Contractions

71. Resistance and Speed of Contraction

73. Muscle Power
Maximal power occurs where the product of force (P) and velocity (V) is greatest (P=FV)
Max Power= 4.5units X

74. _______ refer to muscle contractions
that produce a shortening muscle with
a constant contraction strength at a
given load.
Treppe contractions
Isotonic contractions
Twitch contractions
Isometric contractions

75. Section 2. Motor Unit
a single motor neuron (a motor) and all (extrafusal) muscle fibers it innervates
the physiological functional unit in muscle (not the cell)
All cells in motor unit contract synchronously

76. Extrafusal Muscle: innervated by Alpha motor neuron
Intrafusal muscle: innervated by Gamma motor neurons

77. Motor units and innervation ratio
Fibers per motor neuron
Extraocular muscle 3:1
Gastrocnemius 2000:1
（腓肠肌）
Purves Fig. 16.4

78. The muscle cells of a motor unit are not grouped, but are interspersed among cells from other motor units
The coordinated movement needs the activation of several motors

80. Overview - organization of motor systems
Motor Cortex
Brain Stem
Spinal Cord
-motor neuron
Final common pathway
Skeletal muscle

81. Final common path - -motor neuron
(-)
muscle
fibers
(+)
(-)
axon
hillock
motor nerve
fiber
NM junction
Schwann
cells
Receptors?
acetylcholine
esterase
Transmitter?

82.   Final Common Pathway,
a motor pathway consisting of the motor neurons by which nerve impulses from many central sources pass to a muscle in the periphery

83. Smooth, sustained muscle contractions in vivo are due to synchronous activation of motor units
True
False