1. The Sliding Filament Theory
“How Do Muscles Contract?”

2. The Sliding Filament Theory
This theory states that during contraction, the thin filaments slide pass the thick filaments so that they over lap by a greater degree.

3. Sliding Filament Model
The result is that the I bands shorten and the distance between the Z discs decrease.
The H band disappears and the A bands remain the same length.

4. 1 2 Z H I A Fully relaxed sarcomere of a muscle fiber
Fully contracted sarcomere of a muscle fiber A Z H 1 2

5. The Sliding Filament Theory
For a muscle to contract, three events need to occur: a) The muscle needs to be stimulated by a nerve ending. This leads to a change in the membrane potential. The site of this is called the neuromuscular junction.

6. The Sliding Filament Theory
For a muscle to contract, three events need to occur: b) An electrical current (action potential) then needs to be generated along the sarcolemma.

7. The Sliding Filament Theory
For a muscle to contract, three events need to occur: c) The electrical current results in the final trigger which is a short lived rise in intracellular calcium ions which results in the in the contraction.

8. The Neuromuscular Junction
The nerve cells that activate skeletal muscle fibers at the neuromuscular junction called somatic (body) motor (think muscles) neurons.

9. The Neuromuscular Junction
The motor neurons reside in the spinal column and brain, they have long cyctoplasmic extensions called axons.

10. The Neuromuscular Junction
The motor neurons reside in the spinal column and brain, they have long cytoplasmic extensions called axons.
These enter the muscle and divide extensively so that each muscle fiber (cell) has its own axon terminal which forms a neuromuscular junction.

11. Figure 9.13 A motor unit consists of a motor neuron and all the muscle fibers it innervates.
Spinal cord
Motor neuron
cell body
Muscle
Branching axon
to motor unit
Nerve
Motor
unit 1
unit 2
fibers
axon
Axon terminals at
neuromuscular junctions
Axons of motor neurons extend from the spinal cord to the muscle.
There each axon divides into a number of axon terminals that form
neuromuscular junctions with muscle fibers scattered throughout
the muscle.
terminals form
neuromuscular
junctions, one per
muscle fiber (photo-
micrograph 330x).
(b)
(a)

13. The Neuromuscular Junction
The axon does NOT come into direct contact with the sacrolemma of the muscle fiber. T
There is a 1 to 2 nm cleft between them called the synaptic cleft. This cleft is not empty but is filled with a gel like extracellular matrix.

15. The Neuromuscular Junction
The nerve impulse is transmitted across this cleft by the release of a neurotransmitter.
This crosses the space and attaches to specific membrane receptors on the sacrolemma.

17. The Neuromuscular Junction
The typical neurotransmitter found at these synaptic junctions is acetylcholine.

18. The Neuromuscular Junction
This molecule resides is vesicles in the axon and is released upon depolarization of the axon terminal.

19. The Neuromuscular Junction
These diffuse across the cleft and attach to receptors which then stimulate the depolarization of the muscle fiber.

20. The Neuromuscular Junction
Recall that all cells are polar, they are positively charged on the outside and negatively charged on the inside.
Sodium ions, Na+ are in high concentration on the outside and potassium ions, K+, are in high concentration on the inside.

21. The Neuromuscular Junction

22. The Neuromuscular Junction
Acetylcholine binds to its receptor on the sarcolemma and a gated ion channel is opened. This causes sodium ions to diffuse into the muscle fiber and potassium ions to diffuse out.

23. Myasthenia Gravis
This is an autoimmune disease that specifically attacks the acetylcholine receptor.
Symptoms include:
Weakness starting with the eye lids (ptosis)
Progressing to a general weakness
Ends with difficulty swallowing and SOB

24. Paralytic Drugs
Curare competitively binds to the acetyl choline receptor but does not lead to depolarization.
Death from asphyxiation quickly follows

26. Figure 9.8 Events at the Neuromuscular Junction (2 of 4)1
Action potential
arrives at axon terminal
of motor neuron.
Ca2+
Ca2+ 2
Voltage-gated Ca2+
channels open and
Ca2+ enters the axon
terminal.
Synaptic vesicle
containing ACh
Mitochondrion
Axon terminal
of motor neuron
Synaptic cleft 3
Ca2+ entry
causes some
synaptic vesicles
to release their
contents
(acetylcholine)
by exocytosis.
Fusing
synaptic
vesicles
ACh 4
Junctional
folds of
sarcolemma
Acetylcholine, a
neurotransmitter, diffuses
across the synaptic cleft
and binds to receptors in
the sarcolemma.
Sarcoplasm of muscle fiber

27. Figure 9.8 Events at the Neuromuscular Junction (3 of 4)
Postsynaptic mem-
brane ion channel
opens; ions pass.
Na+ K+ 5
ACh binding opens ion channels that allow
simultaneous passage of Na+ into the muscle
fiber and K+ out of the muscle fiber.

28. Generation and Propagation of the Action Potential
The initial depolarization at the neuromuscular junction ignites an action potential that spreads out in all directions across the sarcolemma.
The depolarization opens voltage- gated sodium channels.

29. Generation and Propagation of the Action Potential
As the polarization moves down the sarcolemma, other voltage gated channels are opened and the process continues.

30. Local depolarization: generation of the end plate potential on the
Figure 9.9 Summary of events in the generation and propagation of an action potential in a skeletal muscle fiber.
Na+ K+
Axon terminal
Synaptic
cleft
ACh–
ACh 1
Local depolarization:
generation of the end
plate potential on the
sarcolemma
Open Na+
Channel
Closed Na+
Closed K+
Open K+ 2
Generation and propagation of
the action potential (AP) 3
Repolarization
Sarcoplasm of muscle fiber

31. Repolarization This process restores the resting potential.
The sodium channels initially opened by the depolarization close and at the same time a potassium channel opens, letting potassium to diffuse out of the cell, restoring the negative voltage inside the muscle fiber.

32. Na+ channels close, K+ channels open Depolarization due to Na+ entry
Figure Action potential scan showing changes in Na+ and K+ ion channels.
Na+ channels
close, K+ channels
open
K+ channels
close
Repolarization
due to K+ exit
Threshold
Na+
channels
Depolarization
due to Na+ entry

33. Muscle Fiber Contraction: Cross Bridge Activity
Before the muscle fiber contracts, there has to be an excitation coupling.
This is the sequence of steps where the action potential along the sarcolemma leads to changes in the levels of calcium ions which results in the mechanical contraction.

34. Sarcoplasmic Reticulum and T Tubules
These are two sets of intracellular tubules that participate in the regulation of muscle contraction and excitation coupling.

35. T Tubules
These are found at each A and I band junction. A T-tubule (or transverse tubule), is a deep invagination of the plasma membrane (sarcolemma). These invaginations allow depolarization of the membrane quickly to the interior of the cell.

36. Sarcoplasmic Reticulum (SR)
This is a modified smooth endoplasmic reticulum. Its tubules run longitudinally surround each myofibril. They communicate with each other in the H zone. They function to store calcium ions.

37. Figure 9.11 Excitation-Contraction Coupling (1 of 4)
Axon terminal
of motor neuron
Muscle fiber
Triad
One sarcomere
Synaptic cleft
Setting the stage
Sarcolemma
Action potential
is generated
Terminal cisterna of SR
ACh
Ca2+

38. Figure 9.11 Excitation-Contraction Coupling (3 of 4)
Calcium
ions are
released.
Steps in
E-C Coupling:
Terminal
cisterna
of SR
Voltage-sensitive
tubule protein
T tubule
Ca2+
release
channel
Sarcolemma
Action potential is
propagated along the
sarcolemma and down
the T tubules. 1 2

39. Actin and Myosin & Contraction
Myosin makes up the thick filament. This is a complex molecule that consists of two heavy and four light polypeptides. These form a molecule with a rod like tail with two flexible globular “heads”.

40. Figure 9.3 Composition of thick and thin filaments (2 of 3).
Flexible hinge region
Tail
Myosin head
ATP-
binding
site
Heads
Actin-binding sites
Thick filament
Each thick filament consists of many myosin molecules
whose heads protrude at opposite ends of the filament.
Portion of a thick filament
Myosin molecule

41. Actin and Myosin & Contraction
Actin makes up the bulk of the thin filament. This molecule has ”kidney shaped” polypeptide subunits called globular actin or G actin which combine with the myosin head during the contracting process.

42. Actin and Myosin & Contraction
Troponin is a globular three polypeptide complex. It has several regulatory roles with actin.  
TnI binds to actin
TnT binds to Tropomyosin and helps to position it on actin
TnC binds calcium ions.

43. Other Proteins
Tropomyosin a rod shaped protein which helps to stabilize the actin molecule. In a relaxed muscle fiber, they block myosin blinding sites on the actin molecule.

44. Figure 9.3 Composition of thick and thin filaments (3 of 3).
Tropomyosin
Troponin
Actin
Active sites
for myosin
attachment
Actin subunits
Thin filament
A thin filament consists of two strands of actin subunits
twisted into a helix plus two types of regulatory proteins
(troponin and tropomyosin).
Portion of a thin filament

45. Figure 9.3 Composition of thick and thin filaments (1 of 3).
In the center of the sarcomere, the thick filaments
lack myosin heads. Myosin heads are present only
in areas of myosin-actin overlap.
Longitudinal section of filaments within one
sarcomere of a myofibril

46. Thick filament (myosin) Myosin heads
Figure 9.4 Transmission electron micrograph of part of a sarcomere clearly showing the myosin heads forming cross bridges that generate the contractile force.
Thin filament (actin)
Thick filament (myosin)
Myosin heads

47. Other Proteins
Titin is the primary protein found in the elastic filament.
This protein extends from the Z disc to the thick filament.
It helps the muscle spring back to its original shape after stretching.

48. The Role of Calcium
The cross bridge formation is the attachment of the myosin heads to the actin.
This process requires calcium ions.
Calcium is the key ion in the contraction process.

49. The Role of Calcium
The muscle is relaxes when there are low levels of intracellular calcium ions.
The myosin binding sites on the actin molecule are blocked by Tropomyosin proteins.

50. The Role of Calcium
As intracellular calcium levels rise, the ions bind to regulatory sites on the protein troponin.
This results in a change in troponin’s shape causing it to move the Tropomyosin off the myosin binding sites.

51. Process of movement
Myosin heads bind to the passive actin filaments at the myosin binding sites.

52. Process of movement
Myosin heads bind to the passive actin filaments at the myosin binding sites.
Upon strong binding, myosin and actin undergo an isomerization (myosin rotates at the myosin-actin interface) extending an extensible region in the neck of the myosin head.

53. Figure 9.12 Cross Bridge Cycle (1 of 4)
Actin
Cross bridge formation.
Ca2+ 1
Myosin
head
Thick filament
Thin filament
ADP P i

54. Figure 9.12 Cross Bridge Cycle (2 of 4)
The power (working) stroke. 2
ADP P i

55. Process of movement
3. Shortening occurs when the extensible region pulls the filaments across each other (like the shortening of a spring). Myosin remains attached to the actin.

56. Process of movement
3. Shortening occurs when the extensible region pulls the filaments across each other (like the shortening of a spring). Myosin remains attached to the actin.
4. The binding of ATP allows myosin to detach from actin. While detached, ATP hydrolysis occurs "recharging" the myosin head. If the actin binding sites are still available, myosin can bind actin again.

57. Figure 9.12 Cross Bridge Cycle (3 of 4)
Cross bridge detachment. 3
ATP

58. Figure 9.12 Cross Bridge Cycle (4 of 4)
Cocking of myosin head. 4
ATP
hydrolysis
ADP PI

59. Figure 9.7 The phases leading to muscle fiber contraction (1 of 2).
Muscle fiber is
stimulated by motor
neuron (see
Figure 9.8).
Action potential (AP) arrives at axon
terminal at neuromuscular junction
ACh released; binds to receptors
on sarcolemma
Ion permeability of sarcolemma changes
Local change in membrane voltage
(depolarization) occurs
Local depolarization (end plate
potential) ignites AP in sarcolemma

60. Figure 9.7 The phases leading to muscle fiber contraction (2 of 2).
AP travels across the entire sarcolemma
AP travels along T tubules
SR releases Ca2+; Ca2+ binds to
troponin; myosin-binding sites
(active sites) on actin exposed
Myosin heads bind to actin;
contraction begins
Phase 2
Excitation-contraction
coupling occurs (see
Figures 9.9 and 9.11).

61. Rigor mortis
Illustrates the cross bridging requires ATP.

62. Rigor mortis Illustrates the cross bridging requires ATP.
Most muscles stiffen 3 to 4 hours after death.

63. Rigor mortis Illustrates the cross bridging requires ATP.
Most muscles stiffen 3 to 4 hours after death.
Calcium leaks into the cells, causing cross bridging.

64. Rigor mortis Illustrates the cross bridging requires ATP.
Most muscles stiffen 3 to 4 hours after death.
Calcium leaks into the cells, causing cross bridging.
ATP is no longer being produced, leaving the muscles stiff.

65. Rigor mortis
Rigor mortis disappears after the muscle proteins begin to break down.