1. Muscular System Part B

2. Muscular mechanics

3. The minimal or smallest amount of stimulation that causes the muscle to contract is called the threshold stimulus.
When a muscle cell receives a threshold stimulus, it contracts to its full extent – an all-or-none response.

5. Give a series of identical stimuli - series of twitch contractions with complete relaxation in between contractions
Strength of contractions increases slightly each time – staircase effect or treppe

6. Time

8. Contraction period – 10 – 100 milliseconds
Latent period – Ca++ is released, filament movement takes up slack – 2 milliseconds
Contraction period – 10 – 100 milliseconds
Relaxation period - 10 – 100 milliseconds
Refractory period – time after a contraction until the muscle is able to respond to a second stimulus.
Skeletal muscle – 5 msec
Cardiac muscle – 300 msec (0.3 sec)

9. When stimuli do not allow muscle to relax completely between contractions, the muscle contraction becomes sustained.
If stimulation is great enough, get a sustained contraction called a tetanic contraction or tetanus.

10. Sustained contraction
Tetanic contraction

11. Muscle fiber length

12. Whole muscle myogram
A brief, single stimulus results in a twitch contraction.
A twitch is a brief contraction of all the muscle fibers in a motor unit.

13. When a motor neuron fires, all of its muscle fibers contract fully.
Some motor units are more easily stimulated than others.
If only some of the motor units in a muscle contract, the entire muscle contracts partially.
The process of adding more motor units for a greater muscle contraction is called recruitment or multiple motor unit summation.

14. To prevent fatigue, there is asynchronous recruitment of motor units.
Recruitment varies with the type of muscle fibers.
Muscles maintain a firmness at rest called muscle tone .

15. Types of muscle contraction
Isotonic contraction (iso = same, tonus = tension) results in movement at a joint
Because shortening of the muscle occurs it is called a concentric contraction.
When the muscle lengthens it is called an eccentric contraction.

17. Isometric contraction (iso= same, metric = measure) the force of contraction changes, but the muscle length remains the same.

19. Cardiac Muscle – similar to skeletal muscle in:
Striations – caused by organization of myofilaments
Contains troponin and tropomyosin – site of activation of cross-bridge activity by Ca++
Clear length-tension relationship
Numerous mitochondria and myoglobin (for aerobic respiration)
T tubules and moderately well developed sarcoplasmic reticulum (T tubule at Z line)

20. Cardiac Muscle – differs from skeletal muscle in:
Shorter, larger diameter than skeletal muscle
Branch, forming 3-D networks
Usually only one nucleus
Autorythmicity –influenced by nervous system and hormones
Sarcoplasm is more abundant with more mitochondria
Only one t-tubule per sarcomere

24. Well developed S.R., but less than skeletal muscle; cisternae store less Ca++.
During contraction a lot of Ca++ enters cell from the extracellular fluid in the t-tubule and extracellular fluid around the cell, so extracellular calcium partially controls the strength and length of contraction.
Intercalated discs – desmosomes; gap junctions
Two networks – atria and ventricles – cells contract together linked by gap junctions - functional syncytium

26. Cardiac muscle physiology
Contraction starts at the pacemaker or sinoatrial node.
Autorhythmicity
Contraction due in large part to influx of Ca++ from ECF
Resting potential of -90 mV
Opening of voltage-gated Na+ channels reverses polarity to +30 mV

27. Membrane potential rapidly reverses due to influx of Na+
Plateau phase lasts several hundred milliseconds due to slow influx of Ca++ (and slowing of exit of K+)
Repolarization is due to rapid out flow of K+ ions.
Remains contracted times longer
Long refractory period
Allows for filling of heart chambers
Prevents tetanic contractions

30. In skeletal muscle the amount of Ca2+ released is sufficient to bind all of the troponin molecules
In cardiac muscle only a portion of troponin has bound Ca2+; allows for changes in contractility
In cardiac muscle SR does not release enough Ca2+ to activate muscle contraction.
Ca2+ entering cell during plateau phase triggers release of calcium from SR (calcium-induced calcium release)

31. DHP channels: RyR is 1:1
Release of “calcium sparks” sum to trigger release
Increased cytosolic calcium

33. Removal of Ca2+ from cytosol
Ca2+ATPase in SR runs continuously and is further activated by high cytoplasmic calcium levels (extracellular Ca++ that entered cell can be stored for next contraction)
Also Ca2+ATPase located in sarcolemma
Na+/Ca++ exchange proteins (3:1 ; secondary active transport)

35. Effects of extracellular K+ on heart
Changes in K+ in ECF alter the concentration gradient across sarcolemma
Leads to ectopic foci and cardiac arrhythmias
Decrease in action potential leads to weak contractions and dilation of heart
At extremes, heart can stop

36. Effects of extracellular Ca++ on heart
Rise in ECF Ca++ increases strength of contraction by prolonging plateau phase
Tends to contract spastically
Drugs can influence Ca++ movement across sarcolemma (calcium channel blockers, digitalis e.g.)

37. Inotropy Positive inotropes increase contractility of heart
Sympathetic nervous system stimulation
Catecholamine hormones (epinephrine)
Digitalis
Increased heart rate
Negative inotropes decrease contractility
Decreased heart rate
Coronary artery disease
Certain drugs (calcium channel blockers)

38. Starling’s Law
Within certain physiological limits, an increase in the stretching of the ventricles causes an increase in the force of contraction of the heart.
This allows for instantaneous regulation of contraction for increases in blood entering heart

39. Smooth muscle Nonstriated and involuntary
Cells smaller than skeletal muscle cells
Spindle-shaped
Single nucleus
NO T tubules
Different arrangement of myofilaments
Thin, thick and intermediate filaments

41. Smooth muscle Thick and thin filaments not arranged in sarcomeres
Thick filaments are longer than in skeletal muscle
Thin filaments lack troponin
10-15 thin filaments/ thick (skeletal 2:1)
Intermediate fibers act as cytoskeleton
Typically less SR than in skeletal muscle
Intermediate filaments attach to dense bodies ( act like Z discs)

42. Intermediate fibers connect dense bodies
Thick- and thin-filament contractile units oriented slightly diagonally in a diamond-shaped lattice pattern
Contraction causes the lattice to decrease in length and expand from side to side.

44. During contraction, the sliding thick and thin filaments generate tension that is transmitted to the intermediate filaments, which pull on the dense bodies in the sarcoplasm and those attached to the sarcolemma.
Isolated smooth muscle cells contract by twisting into a helical shape, but this is prevented in intact tissues due to their attachment to other cells.

45. Gap Junctions Often connect smooth muscle cells
May be temporary, and may be under hormonal control
The electrical joining of smooth muscle cells is the basis for classifying smooth muscle into two types:
Visceral (single-unit) smooth muscle
Many cells acting together
Multiunit smooth muscle
Cells contract in small groups

46. Single-unit smooth muscle
Multiunit Smooth Muscle

47. Visceral (single-unit) smooth muscle
More common type
Wrap-around sheets
Fibers form networks that contract together
Connected by gap junctions
Some cells also have autorhythmicity
Largely responsible for peristalsis

48. Multiunit Smooth Muscle
Individual fibers within motor units; few gap junctions
In walls of large arteries, large airways, arrector pili, iris muscles and ciliary body in eye.
Contracts only after stimulation by motor neuron or hormones

49. Physiology of Smooth Muscle
Contractions start slower and last longer
Can shorten and extend to greater extent
Resting potential is much lower and can vary over time due to automatic cyclical changes in the rate at which Na+ is pumped across the membrane.
“Slow wave”

50. Sodium is not the major carrier of current during an action potential, instead it is Ca2+ which enters through voltage-gated channels
Also have receptor-activated or chemically activated Ca2+ channels
Repolarization due to outflow of K+ though voltage-gated channels and some channels sensitive to intracellular Ca2+ levels

52. Physiology of Smooth Muscle
Calcium ions come from the small amount of S.R. and from extracellular fluid through DHP channels
Instead of troponin, contains calmodulin which regulates contraction
Myosin-linked regulation
Camodulin binds with Ca++ and activates myosin light chain kinase (MLCK)

53. ATP for actual contraction is separate
MLCK uses ATP to add a phosphate group to the myosin head. Myosin can then bind to actin
ATP for actual contraction is separate
Enzymes work slowly (100 x slower than skeletal muscle)
Calmodulin is sensitive to Ca2+ conc. in ICF
At 10-7 M Ca2+ , no calcium is bound
At 10-4 M Ca2+ all 4 calmodulin sites are bound and rate of phosphorylation is maximal
In between see gradations in contractile force

56. Relaxation of Smooth Muscle
When Ca2+ levels fall, calmodulin is no longer active and phosphorylation of myosin is reversed by the enzyme myosin light-chain phosphotase (MLCP)

58. Ca2+ also leaves the cell slowly, which delays relaxation and provides for smooth muscle tone.
Sustained tone is important, and in some cases smooth muscle can maintain a low level of active tension for long periods of time; a long sustained contraction is called tonus rather than tetanus

59. Regulation of Smooth Muscle contraction
Responds to signals from autonomic nervous system ( responds to ACh and norepinephrine)
Some have no nerve supply and depolarize spontaneously or to ligands that bind to G protein linked receptors
Many also contract or relax in response to stretching, hormones or local factors (such as changes in pH, oxygen or carbon dioxide levels, temperature or ion concentration).
Enhances or inhibits entry of Ca2+

60. Origin and Insertions
Origin – the attachment of a muscle to the less movable part (torso, etc.)
Insertion – the attachment of a muscle to the more movable part

62. Interactions of muscles
Prime mover – the muscle primarily responsible for a movement
Synergist – stabilizes or assists prime mover
Antagonist – opposes action of prime mover and must relax for prime mover to contract completely

63. Major muscles will be covered in lab.

64. Life Span Changes Develops from mesoderm cells called myoblasts
Multinucleate skeletal muscle cells form through fusion of myoblasts to form myotubes
Fibers are contracting at 7 weeks
ACh receptors sprout over surface of myoblast
Agrin released by nerve endings stimulates clustering of ACh receptors

65. Remaining receptor sites dispersed
Electrical activity in the motor neurons plays a critical role in maturation of muscle fibers
The number of fast and slow fiber types is determined.
Myoblasts producing cardiac and smooth muscle fibers do not fuse. Both develop gap junctions early. Cardiac muscle is pumping blood 3 weeks after fertilization.

66. Repair of muscle
Skeletal and cardiac muscle cells stop dividing early, but retain ability to lengthen and thicken in a growing child and to hypertrophy in adults.
After first year, growth of skeletal muscle is by hypertrophy.
Enlarged fibers may split down middle
Satellite cells (stem cells)repair injured fibers and may allow a very limited regeneration of fibers.
Most repair by fibrosis

67. Repair of cardiac muscle
Cardiac fibers do divide at a modest rate.
Injured heart muscle repaired mostly by fibrosis (scar tissue).
Fibers can hypertrophy and enlarge heart

68. Repair of Smooth Muscle
Limited to good capacity for division and regeneration throughout life
Some increase due to hyperplasia
New fibers can arise from pericytes (stem cells)
Proliferate in atheroscerolsis

69. Development At birth movements are uncoordinated and reflexive
Develops head-to-toe and proximal-to-distal
Through childhood control becomes more sophisticated.
Early hand dominance
Midadolescence reach peak of natural neural control of muscles

70. Male vs. Female Strength has a biological basis Women 36% muscle
Primarily due to effects of testosterone
Strength per unit mass is the same in both sexes

71. Aging changes
Connective tissue and fat increase and there is a slow, continuous reduction in the number of muscle fibers and loss of strength.
At age 30 sarcopenia begins to occur as proteins degrade faster than they are replaced. (regulatory molecules?)
Up to 30% of muscle fibers may be lost by age of 80.

72. Loss of fibers reduces size of motor units
More motor units must be recruited to move a given weight, so requires more effort.
Fast-twitch glycolytic fibers atrophy earlier than slow-twitch oxidative fibers.
Posture not affected until very late in life.
Reduction of ability of muscle to adapt to exercise.
Some loss is disuse atrophy

73. Impairment of synthesis of new muscle proteins
Reduction in nerve activity due to changes in nervous system
Loss of motor neurons
Reduction in synthesis of ACh
Contributes to muscle fiber atrophy and efficiency of stimulation