Muscle Physiology – outline notes

Muscle tissue – (myo, mys, sarco)
-skeletal – striated, voluntary
-smooth – visceral, nonstriated, involuntary
-cardiac – heart, striations, involuntary

Skeletal Muscle
Functions
-movement
-cardiac – blood
-smooth – peristalsis
-skeletal – gross movements
-posture  / stabilize joints
-generates heat


As an organ
-C.T.
-blood vessels
-nervous tissue
-skeletal muscle fibers (cells) / (myofibers)
C.T. wrappings – all cont. with each other and tendons
-endomysium – areolar C.T.; wraps each muscle fiber (muscle cell)
-perimysium – collagenic sheath; wraps a bundle of muscle fibers
-fascicle
-epimysium – dense fibrous C.T.

Blood vessels/nerve supply
-arteries – supply oxygen and nutrients
-veins – carry away waste

-each muscle cell has individual innervation

Microanatomy of skeletal muscle cells
-embryonic development
-myoblasts fuse and form large, multinucleated muscle cells
-satellite cells – myoblasts that do not fuse; may fuse after injury

-sarcolemma – cell membrane

-sarcoplasm – cytoplasm
-stored glycogen
-myoglobin – stores oxygen; red pigment
-other normal organelles
-Modified organelles
-myofibrils
-sarcoplasmic reticulum
-T-tubules

Myofibrils
-80% of cell volume; thousands/cell
-rod-like; extend the length of the cell
-sarcomeres – smallest contractile units; thousands make up myofibril

Sarcomeres
-Z-line to Z-line
-Z-line – consists of connectin (protein); connects thin
(myo)filaments
-A-band – DARK band; thin and thick filaments; length of thick filament
-H zone – lighter stripe in A band; only thick filaments
-M line – bisects H zone; darker line; connects thick filaments
-I band – LIGHT band; thin filaments

Thick filaments
-protein – myosin (several hundred myosin molecules / thick filament)
-tails – point toward M line
-head (cross-bridges) – interact with thin filaments
-ATP binding sites and ATPase
-ATP —-ADP and PO43-
-hinge region
-titin – the core of filament that continues to Z – line; elastic properties

Thin filaments
–proteins – actin, tropomyosin, troponin
-actin
-F actin – 2 twisted strands composed of G actin (fibrous)
-G actin – active sites where myosin heads bind (globular)
(2 strings of pearls)
-tropomyosin
– coils w/ F actin; blocks 7 active sites; relaxed muscle
-troponin – 3 polypeptide subunits
-TnI – binds to G actin; inhibitory
-TnT – binds 1 troponin to 1 tropomyosin
-TnC – binds Calcium
Sarcoplasmic reticulum (SR)
-interconnecting membrane tubule complex; similar to sER
-surrounds each myofibril (loosely crocheted sweater around your arm)
-most run longitudinal w/ myofibril
-some form perpendicular cross channels over A-I junction
– terminal cisternae – occur in pairs
-Control intracellular Calcium; store it and release it on demand
-high [Ca2+] in SR; low [Ca2+] in sarcoplasm

T-tubules (transverse tubules)
-sarcolemma penetrates at each A-I junction
-protrudes b/t each pair of terminal cisternae = triad
-relationship b/t SR and t-tubule(sarcolemma)
-allow for communication deep within the myofiber

Muscle Contraction
-When muscle cells contract, myofilament do not shorten
-Sliding Filament Theory – Huxley 1954
-thin filaments slide centrally past thick filaments
-Z-lines are pulled closer
-I band and H zone shortens
-width of A band remains constant

Steps of Contraction
Step 1 *Actin Binding Sites Exposed
-muscle cell stimulated; causes SR to release Calcium into the cell
-calcium binds to TnC of troponin; troponin changes conformation
and pulls tropomyosin exposing binding sites

Step 2 *Cross Bridge Attachment 
-myosin heads attracted to binding sites and cross bridge
attachment occurs

Step 3 *Power Stroke
-myosin heads configuration changes; heads bend and pull thin
filaments centrally (Power Stroke)
-heads release ADP and PO43- (low energy state)

Step 4  *Cross Bridge Detachment
-ATP binds to the myosin head and loosens attachment

Step 5 *Cocking of Myosin Head / Reactivation
-hydrolysis of ATP; returns head to cocked position (high energy
state of myosin head); like a coiled spring
-ADP and Phosphate remain attached until the next power stroke

-when calcium is reclaimed by SR –– contraction ceases
-one power stroke shortens muscle ~1%
-Contraction is 30-35% of resting muscle
-Rigor Mortis
-the body stops producing ATP
-Calcium invades sarcoplasm —– contraction
-no cross-bridge detachment without ATP
-15-25 hours later myofilaments break down

Neuromuscular junction
-axons of motor neurons innervate skeletal muscle
-neuromuscular junction – the site where one axon ending innervates one
muscle fiber
-synaptic cleft – space b/t axon ending and muscle cell
-filled with basal lamina – gel-like substance
-within axon ending (synaptic terminal)
-synaptic vesicles – membrane sacs that contain
acetylcholine (ACh); a neurotransmitter
-motor end plate – highly folded region on sarcolemma that
contains ACh receptors; at the neuromuscular junction
-acetylcholinesterase (AChE, or cholinesterase) – found in synaptic
cleft and sarcolemma; breaks down ACh

Neuron stimulation
Step 1  *Release of ACh from the synaptic terminal into the synaptic cleft
-action potential (electrical impulse) reaches the synaptic terminal
-Calcium rushes in; synaptic vesicles release ACh via exocytosis

Step 2  *ACh diffuses across the synaptic cleft and binds to ACh receptors
on sarcolemma

Step 3  *Action potential generated on the sarcolemma
-electrical impulse spreads across sarcolemma and down t-tubules
at triad
Step 4  *SR releases Calcium

Step 5 Calcium binds to troponin
-Muscle contraction occurs

Excitation-Contraction Coupling – action potential across t-tubules cause SR to release calcium and start muscle contraction

ATP dependent Calcium pumps – immediately pump calcium back into SR
-Calcium levels fall in the sarcoplasm
-Calcium detaches from troponin
-tropomyosin covers active sites
-contraction ends

AChE – breaks down ACh to stop signal

Muscle Mechanics

Tension – single muscle fiber
-depends on the number of cross-bridge interactions (length)
-muscle fiber at any given length (determines overlap of filaments) will
always produce the same tension
-muscle fiber is “on” or “off”

**Tension produced by a muscle depends on
-number of fibers activated
-frequency of stimulation

Muscle Metabolism
-Muscle contraction requires ATP
-detachment of head
-cross bridge movement
-control of calcium pump in SR
-7300 calories of energy/mole of ATP; stored in high energy bonds

Muscle has ~ 3 sec. of stored ATP

3 pathways to generate ATP during muscle activity

1. Creatine Phosphate (CP)
-stored in muscle
-has high energy phosphate bond
-CP + ADP —– ATP + creatine
-creatine phosphokinase (CPK or CK)
-enzyme catalyzes the reaction
-find in high levels in the blood when muscle cells are damaged
-muscle at rest replenishes CP
-creatine + ATP —– CP + ADP
-phosphagen energy system
-stored ATP + CP = 8 – 10 seconds of maximal muscle power

2. Glycogen – Lactic Acid system
-Anaerobic, peak muscle activity
-glycogenolysis – store glycogen is split into glucose
-glycolysis – inhibited in the presence of oxygen
–glucose ——– 2 pyruvic acids
-net of 2 ATP production
-with oxygen present
-pyruvic acid ——– 34 ATP in mitochondria
-without oxygen present
-pyruvic acid —– lactic acid
-lactate dehydrogenase
-provides additional 1 ½ minutes of ATP

3. Aerobic System
-at rest, light exercise
-oxygen not limited
-mitochondria metabolizes 2 pyruvic acids to 34 ATP
-also metabolizes fatty acids and amino acids to ATP
-produces much more ATP than the Anaerobic system, but works 2 ½  times
more slowly and requires oxygen

Muscle fatigue
-no contraction despite continued neural stimulation
-exhaustion of ATP and CP (short peak levels of activity)
or
-damage to SR during marathon

Recovery period
-replenish muscle with ATP, glycogen, CP
-Cori cycle
-lactic acid diffuses out of muscle into the blood and to liver
-liver converts lactic acid back to glucose and releases it into the blood.
-muscles absorb glucose