Muscle histology and physiology

Lecture Notes

I. General characteristics of muscle tissue

A. Functional characteristics
1. Excitability - responds to stimuli from nerve impulse or hormones, can carry signal along membrane

2. Contractability (shortening) - able to contract its longest dimension

3. Extensibility (lengthening) - able to extend its longest dimension

4. Elasticity - muscle will return to intermediate length

Describe the functional characteristics of muscle tissue.

B. Types of muscle tissue

1. Skeletal muscle tissue a) Near skeletal system
b) Long muscle cells, multinucleated, many mitochondria, with striations
c) Strong rapid contractions with small groups of cells, generally being under voluntary nervous control

2. Cardiac muscle tissue a. Found in heart
b. Medium-long, 1 nucleus, branched, gap junctions (intercalated disks), with striations
c. Medium strength, rhythmic contractions of large groups of cells under involuntary nervous control

3. Smooth muscle tissue a. Found in hollow visceral organs (digestive system, urinary and gall bladders, uterus) as well as blood vessels and bronchioles in lungs.
b. Short, spindle-shaped, 1 nucleus with gap junctions, no striations
c. Weak, sometimes rhythmic, contractions of large layers of cells under autonomic nervous control
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Compare and contrast the structural and functional characteristic of different muscle tissue types. 
 C. Functions of muscular system 1. Motion (move body and fluids)

2. Maintain posture, joint support (no movement)

3. Heat production

II. Muscle gross anatomy (organ) A. Relationship with skeletal system

1. muscles typically pass over joint, e.g., brachialis

2. origin - least moveable attachment site e.g., humerus

3. insertion - most moveable attachment site e.g., ulna

4. action - movement of body part e.g., flex forearm

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B. Cross section of muscle (organ)

1. Muscle and connective tissue a. Each muscle cell surrounded by endomysium
b. Group of cells (fasicle) connected together by perimysium
c. Entire muscle covered by epimysium which continues as tendons

 FUNCTION of above connective tissues is to transmit force of muscular contractions to attachment sites
See this video for some clarification.

2. Nerves and blood vessels (neurovascular bundle)
Create list of structures that connect periosteum of bone to muscle cell membrane. Describe the function of that group of structures/tissues.

III. Skeletal Muscle cell histology A. Cell (end to end of muscle) 1. Sarcolemma (muscle cell membrane) spreads throughout cell interior (as transverse tubules) allowing electrical signals to trigger the sarcoplasmic reticulum (which releases Calcium)

2. Many mitochondrion (need lots ATP)

3. Sarcoplasm ( or muscle cell's cytoplasm)

4. sarcoplasmic reticulum ( or muscle cell's endoplasmic reticulum)
 contains Ca++ ions that are released upon receiving electrical signal.

5. Myofibrils (100-1000's/cell) rod-like structures that contain contractile elements and are  surrounded by transverse tubules and SR

B. Myofibril structure 1. Myofibrils consist of two types of overlapping contractile protein structures (=filaments):
 actin (thin) filament
 myosin (thick) filament

2. Filaments are arranged into linearly repeating contractible units (sarcomeres), individual filaments do not reach from sarcomere end to end.
   

C. Sarcomere -contractile unit of muscle cell
1. Sarcomere limits defined by pair of Z discs (place where actin filaments are anchored to each other)

2. Actin filaments stretch inward from each end of sarcomere (both Z discs) towards center of sarcomere thereby overlapping (but not connected to) myosin filaments

3. Myosin filaments reside in center of sarcomere and anchored to each other at M line

Overlap of different filaments produce dark bands (in center where actin and myosin filaments overlap) and light bands ( where there is only actin near Z discs). This light/dark/light appearance explains striations.
 D. Filaments 1. Actin filament (thin ) a. Actin protein molecules
 each globular molecule has binding site for myosin crossbridges (on myosin molecules of thick filament)

b. Troponin and tropomyosin regulatory molecules
 Ca++ binds to thread-like, regulatory molecules, changing their shapes, thereby uncovering myosin binding site on actin molecules
 

2. Myosin filament (thick) a. Myosin proteins (shaped like golf clubs) have crossbridge ends (club ends)
b. Crossbridges have binding site for actin molecules
c. Crossbridges also have ATP binding site -when ATP binds to myosin then the myosin changes shape from low energy shape to high energy shape. Shape change powers movement during contraction.
d. Crossbridges cannot bind to actin and ATP at same time.
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IV. Physiology of single motor unit contractions (motor unit is bunch of muscle cells stimulated by single motor neuron)

A. Excitation (signal to cause cell to contract)

1. Electrical signal (nervous action potential ) arrives from brain, carried down the membrane of the spinal cord neuron, to motor neuron membrane near muscle cells (neuromuscular junction)

2 Neurotransmission at neuromuscular junction Note: Motor neuron membrane and muscle cell membrane (sarcolemma) are adjacent but DO NOT touch-this gap is known as the synaptic cleft.
Note: action potential (signal or impulse) can only travel along membranes.
a. Electrical signal travels to end (axon terminal membrane) of motor neuron.
b. signal causes inflow of calcium into neuron, causing release of neurotransmitter (in this case, Acetylcholine).
c. neurotransmitter chemical (acetylcholine or ACh) diffuses across cleft, from motor neuron membrane to sarcolemma

3. Acetylcholine reaches sarcolemma and triggers new electrical signal (muscle action potential)
4. New electrical signal travels across sarcolemma, down T tubules into interior of the muscle cell.
5. Signal at T tubules causes release of Ca++ from Sarcoplasmic reticulum (SR)
6. Calcium binds to Troponin/Tropomyosin to begin contraction cycle.

B. Contraction cycle
(starts with Ca++ ions diffusing from sarcoplasmic reticulum into myofibrils to bind with troponin/tropomyosin regulatory proteins that covers actin binding sites on myosin.. Binding changes regulatory proteins shape causing the myosin-binding sites on actin molecule to be uncovered allowing myosin to bind with actin).

1. ATP hydrolysis -(ADP + P) releases energy forcing myosin to high energy (cocked) position.

2. Crossbridge attachment-Myosin binding with actin

3.Power stroke- attachment promotes change in shape of myosin from high energy to low energy shape. movement of myosin crossbridge moves actin towards center of sarcomere shortening the sarcomere length.

4. Cross bridge detachment- ATP binding to crossbridge detaches the myosin cross bridges from actin

Start cycle again with above ATP hydrolyzing and providing energy to force myosin back to high energy position.

Contraction cycle continues as long as enough Ca++ and ATP are available. Ca++ ions only released when a signal arrives at the SR. ATP available as long as cell regenerates ATP faster than used.

If no ATP available(death) then cross bridges do not detach causing rigor mortis which occurs about 4-6 hours after death (rigidity gone after 24-36 hours)

B. Relaxation after contraction (when nervous impulses are gone)
1. ACh removed by enzyme (Acetylcholineesterse) in synapse

2. Ca++ actively pumped back into SR by active membrane protein pump

D. Excitation - contraction sequence (Review)

1. Motor Neuron electrical signal travels to its membrane near skeletal muscle cell.

2. ACh, relased by motor neuron, diffuses to sarcolemma and generates new signal at sarcolemma

3. Muscle electrical signal flows across sarcolemma and then down transverse tubules

4. Signal at T tubules causes Ca++ to be released from SR , Myosin already in energized position. (step 1)

5. Ca++ binds with Troponin/ Tropomyosin causing them to move, unblocking binding sites of actin

6. Binding of actin & myosin (step 2)

7. Power stroke(movement of actin over myosin) resulting in contraction (step 3)

8. ATP binding causes detachment of actin/myosin (step 3)

ATP hydrolysis causes myosin back to "cocked" position to continue cycle (back to step 1)
Cycle ends when signals no longer reach the sarcolemma.

Describe, in correct sequence, the entire excitation sequence with special attention to actions at the sarcomere.

V. Muscle contraction

A. Single muscle motor unit response (only one electrical signal stimulus-laboratory preparation only)
Motor units are group of muscle cells that are stimulated at same time by single neuron (can be from 4-1000's muscle cells in one motor unit)
Several to many motor units are found in each muscle.

One electrical signal causes one contraction cycle or "twitch"
All cells in each motor unit contract undergo all or none response.

B. Multiple stimulus of motor unit
Increased rate of stimulations causes twitch's force to add up ( i.e., wave summation) to a smooth and sustained contraction force. This sustained contraction force is called "tetany". Fused tetany is normal manner of contraction resulting in plateau shape.


C. Entire muscle contraction (motor unit recruitment)
A muscle has graded responses (longer duration and/or stronger contractions) rather than twitch (all or none responses)

1.Increased number of motor units recruited at one time (synchronous recruitment) is  major way to increase strength of contraction

2. Asynchronous recruitment (few motor units at one time but constantly replacing others over time) is major way to increase duration of contraction (See illustration below)

Muscle tone is maintained by random excitation of muscles (in an asynchronous way)-this allows muscle to be physiologically ready to contract at any time.

E. Fatigue causes reduction in muscle contraction force

Muscle fatigue results when

1. Intracellular Ca++ levels become abnormal.

2. ATP stores are somewhat diminished.

3. pH drops thereby adversely affecting crossbridge activity

Distinguish between all or none responses and graded responses. Relate your understanding of the terms:twitch,summation, recruitment, and fatiqueVI. Skeletal muscle metabolism
need to replace lost ATP for sustained mucular contractions
A. Energy for contraction from variety of sources 1. Short term sources (anaerobic) in cytosol a) ATP stored in cell
 0 - 6 seconds
 used to detach cross bridges and pump Ca++ back into SR
 needs to be replenished constantly during contractions

b) Creatine phosphate (CP)
 6 - 15 seconds
 CP hydrolysed to give off phosphates to generate creatine and ATP
(CP + ADP =C + ATP)

c) stored glucose
 up to a minute
glycolysis pathway (no O2 required) breaks glucose in cytosol to form pyruvate + little ATP

2. Longer term sources -aerobic pathways (O2 required) in mitochondria

a) Stored glycogen
 up to 30 minutes
 glycogen broken to glucose in cytosol
Kreb's Cycle in mitochondria (O2 required) breaks down pyruvate (from previous glucose catabolism produced by glycolysis) to form CO2 + H2O + lots ATP

b) Triglyceride fats, Fatty acids
30-? minutes
Kreb's Cycle in mitochondria (O2 required) breaks down fatty acids (from breakdown of stored triglycerides) to form CO2 + H2O + lots ATP

Compare and contrast the mechanisms for supplying muscle cells with ATP

3. Compare anaerobic vs aerobic respiration

a) More ATP made in aerobic enzyme pathways over long term
 moderate exertion, long duration activities use aerobic

b) ATP made faster in anaerobic
high exertion, low duration activities use anaerobic
 
 

C. Oxygen debt
 with aerobic metabolism O2 used faster than replaced so an O2 debt is incured
 i.e., amount of O2 needed to oxidize lactic acid back to pyruvate
 build up of lactic acid is source of ache in over-worked muscles

D. Heat production
 much of ATP hydrolysis does not go to muscle contraction but is lost as heat (heat generation)

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Professor Thomas M. Lancraft
Human Anatomy and Physiology Courses
at St. Petersburg College
St. Petersburg/Gibbs Campus

3/2009