Muscle Fiber Anatomy

Sarcolemma - cell membrane Surrounds the sarcoplasm (cytoplasm of fiber) Contains many of the same organelles seen in other cells An abundance of the oxygen-binding protein myoglobin Punctuated by openings called the transverse tubules (T-tubules) Narrow tubes that extend into the sarcoplasm at right angles to the surface Filled with extracellular fluid Myofibrils -cylindrical structures within muscle fiber Are bundles of protein filaments (=myofilaments) Two types of myofilaments 1. Actin filaments (thin filaments) 2. Myosin filaments (thick filaments) At each end of the fiber, myofibrils are anchored to the inner surface of the sarcolemma When myofibril shortens, muscle shortens (contracts) Myofibrils surrounded by sarcoplasmic Reticulum, a calciumcontaining network of tubules

Sarcoplasmic Reticulum (SR)

SR is an elaborate, smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril Form chambers called terminal cisternae on either side of the T-tubules A single T-tubule and the 2 terminal cisternae form a triad SR has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR

Sarcoplasmic Reticulum (SR)

SR is an elaborate, smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril Form chambers called terminal cisternae on either side of the T-tubules A single T-tubule and the 2 terminal cisternae form a triad SR has Ca++ pumps that function to pump Ca++ out of the sarcoplasm back into the SR

Sarcoplasmic Reticulum (SR)

Figure 9.5

Structure of Actin and Myosin

Two strands of fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere. Composed of G actin monomers each of which has an active site Actin site can bind myosin during muscle contraction. Tropomyosin: an elongated protein winds along the groove of the F actin double helix. Troponin is composed of three subunits:
Tn-I site: binds to actin Tn-T site: binds to tropomyosin Tn-C site: binds to calcium ions

Actin (Thin) Myofilaments

The tropomyosin/troponin complex regulates the interaction between active sites on G actin and myosin.

Myosin (Thick) Myofilament

Many elongated myosin molecules shaped like golf clubs. Molecule consists of two heavy myosin molecules wound together to form a rod portion lying parallel to the myosin myofilament and two heads that extend laterally. Myosin heads 1. Can bind to active sites on the actin molecules to form cross-bridges. 2. Attached to the rod portion by a hinge region that can bend and straighten during contraction. 3. Have ATPase activity: activity that breaks down adenosine triphosphate (ATP), releasing energy. Part of the energy is used to bend the hinge region of the myosin molecule during contraction

Sarcomeres

Z disk: filamentous network of protein. Serves as attachment for actin myofilaments Striated appearance
I bands: from Z disks to ends of thick filaments A bands: length of thick filaments H zone: region in A band where actin and myosin do not overlap M line: middle of H zone; delicate filaments holding myosin in place

In muscle fibers, A and I bands of parallel myofibrils are aligned. Titin filaments: elastic chains of amino acids; make muscles extensible and elastic

Striations and Sarcomeres

Nerve-Muscle Relationships
Skeletal muscle must be stimulated by a motor neuron or it will not contract Cell bodies of somatic motor neurons in brainstem or spinal cord
Anterior horn motor neurons (AHMN)

Axons of these AHMNs form terminal branches with synaptic bulbs

Each terminal branch supplies one muscle fiber

Each motor neuron and all the muscle fibers it innervates = motor unit

White Matter: Pathway Generalizations

Descending (Motor) Pathways

Descending tracts deliver motor impulses from the brain to the spinal cord Motor pathways involve two neurons
Upper motor neuron (UMN)
Originates (cell body) in brain Its axons form the projection tracts of the brain Synapses with LMN in spinal cord

Lower motor neuron (LMN): AHMN

Originates (cell body) in anterior horn Myelinated axon exits cord via ventral root and enters spinal nerve Its synaptic knobs form the neuromuscular junction (aka, myoneural junction)

Pyramidal (Corticospinal) Tracts

Originate in the precentral gyrus of brain (aka, primary motor area)
I.e., cell body of the UMN located in precentral gyrus

Pyramidal neuron is the UMN

Its axon forms the corticospinal tract

UMN synapses in the anterior horn with LMN

Some UMN decussate in pyramids = Lateral corticospinal tracts Others decussate at other levels of s.c. = Anterior corticospinal tracts

LMN (anterior horn motor neurons)

Exits spinal cord via anterior root Activates skeletal muscles

Regulates fast and fine (skilled) movements

1.

Corticospinal tracts
1. 2. 3. 4. Location of UMN cell body in cerebral cortex Decussation of UMN axon in pyramids or at level of exit of LMN Synapse of UMN and LMN occurs in anterior horn of s.c. LMN axon exits via anterior root

2. 3. 4.

Motor Units
Def: A motor neuron and all the muscle fibers it innervates
Fibers aredispersed throughout the muscle When contracted together cause a weak contraction over wide area provides ability to sustain long-term contraction as motor units take turns resting (postural control)

Fine control of muscles

small motor units contain as few as 4-6 muscle fibers per nerve fiber Extraocular muscles (move eyeball)

Strength control
Gastrocnemius muscle has 1000-1500 muscle fibers per nerve fiber

Neuromuscular Junctions (Synapse)

Functional connection between nerve fiber and muscle cell Neurotransmitter (acetylcholine/ACh) released from nerve fiber stimulates muscle fiber Components of synapse (NMJ)
synaptic knob is swollen end of axon terminal
contains ACh

Motor end plate: region of sarcolemma that abuts the synaptic knob; highly folded
increases surface area allowing for more ACh receptors contain acetylcholinesterase that breaks down ACh and causes relaxation

synaptic cleft = tiny gap between synaptic knob and sarcolemma of muscle fiber

The Neuromuscular Junction

Muscle Fibers are Excitable

Sarcolemma is polarized or charged
resting membrane potential due to Na+ outside of cell and K+ and other anions inside of cell difference in charge across the membrane = resting membrane potential (-90 mV cell)

Stimulation (ACh binding to cholinergic receptors) opens ion gates in sarcolemma

ion gates open (Na+ rushes into cell and K+ rushes out of cell)
quick up-and-down voltage shift = action potential

spreads over cell surface as an action potential

Muscle Contraction and Relaxation

Four actions involved in this process
Excitation = nerve action potentials lead to action potentials in muscle fiber Excitation-contraction coupling = action potentials on the sarcolemma activate myofilaments Contraction = shortening of muscle fiber Relaxation = return to resting length

Images will be used to demonstrate the steps of each of these actions

Sliding Filament Theory

Explains the relationship between thick and thin filaments as contraction proceeds Cyclic process beginning with calcium release from SR
Calcium binds to troponin Troponin moves, moving tropomyosin and exposing actin active site Myosin head forms cross bridge and bends toward H zone (pulling actin inward) ATP allows release of cross bridge

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

Tension
Created when muscles contract Series of steps that begin with excitation at the neuromuscular junction
Calcium release Thick/thin filament interaction Muscle fiber contraction Tension

Excitation-Contraction Coupling

Sequential Events of Contraction

Myosin head (high-energy configuration)

Thin filament

Myosin cross bridge attaches to the actin myofilament

Thick filament

ADP and Pi (inorganic phosphate) released

4 As ATP is split into ADP and Pi,

cocking of the myosin head occurs

2 Working strokethe myosin head pivots and

bends as it pulls on the actin filament, sliding it toward the M line

Myosin head (low-energy configuration)

3 As new ATP attaches to the myosin head,

the cross bridge detaches

Rigor Mortis
Stiffening of the body beginning 3 to 4 hours after death Deteriorating sarcoplasmic reticulum releases calcium Calcium activates myosin-actin cross-bridging and muscle contracts, but can not relax. Muscle relaxation requires ATP and ATP production is no longer produced after death Fibers remain contracted until myofilaments decay

Functions of ATP in Skeletal Muscle Contraction

1. Hydrolysis of ATP by myosin - energizes the cross-bridges, providing energy for force generation. 1. Binding of ATP to myosin - dissociates cross-bridges bound to actin. 1. Energizes Ca++ pumps that actively transport Ca++ back into the sarcoplasmic reticulum - lowers cytosolic calcium levels leading to relaxation 1. Runs the Na+-K+ pump in the sarcolemma
- maintains the resting membrane potential of the sarcolemma

The Effect of Sarcomere Length on Tension

Amount of tension (force) generated by the muscle depends on length of muscle before it was stimulated
length-tension relationship (see graph next slide)

Overly contracted (weak contraction results) See Fig. 1 on left side on next slide thick filaments too close to Z discs and cant slide

Too stretched (weak contraction results)

Fig. 3 on right side on next slide little overlap of thin and thick filaments does not allow for very many cross bridges too form

Optimum resting length (Lo) produces greatest force when muscle contracts
Fig. 2 in center central nervous system maintains optimal length producing muscle tone or partial contraction

The Effect of Sarcomere Length on Tension

Active tension: force applied to an object to be lifted when a muscle contracts Load - the object being acted upon by the muscle Stretched muscle- not enough cross-bridging Crumpled musclemyofilaments crumpled, crossbridges can't contract

Muscle Twitch
A muscle twitch is the response of a muscle fiber to a single, brief threshold stimulus The three phases of a muscle twitch are:
Latent period (2 msec delay)
No visible contraction occurs; no tension developed Processes of excitation-contraction coupling occurring

Contraction phase
External tension develops as muscle shortens Not all skeletal muscle fibers have same contraction time Fast twitch fibers = 10 msec; Slow twitch fibers = 100 msec

Relaxation phase
Loss of tension and return to resting length as calcium returns to SR

Muscle Twitch
Threshold = voltage producing an action potential a single brief stimulus at that voltage produces a quick cycle of contraction and relaxation called a twitch (lasting less than 1/10 second = 100 msc) A single twitch contraction is not strong enough to do any useful work

Figure 9.13 (a)

The Twitch and the Development of Tension

Effects of Repeated Stimulations

Twitch and Treppe Contractions

Muscle stimulation at variable frequencies

low frequency (up to 10 stimuli/sec)- Fig A above
each stimulus produces an identical twitch response

moderate frequency (between 10-20 stimuli/sec)

each twitch has time to recover but develops more tension than the one before (treppe phenomenon)
calcium was not completely put back into SR heat of tissue increases myosin ATPase efficiency

Incomplete and Complete Tetanus

Higher frequency stimulation (20-40 stimuli/second) generates gradually more strength of contraction (Fig A)
each stimuli arrives before last one recovers
temporal summation or wave summation

incomplete tetanus = sustained fluttering contractions

Maximum frequency stimulation (40-50 stimuli/second) (Fig. B)

muscle has no time to relax at all twitches fuse into smooth, prolonged contraction called complete tetanus rarely occurs in the body

Motor Units
Def: A motor neuron and all the muscle fibers it innervates
Fibers are dispersed throughout the muscle Provides ability to sustain long-term contraction as motor units take turns resting (postural control)

Fine control of muscles

small motor units contain as few as 4-6 muscle fibers per nerve fiber Extraocular muscles (move eyeball)

Strength control
Gastrocnemius muscle has 1200-1500 muscle fibers per nerve fiber

Stimulus Intensity and Muscle Tension

Muscle contracts more vigorously as stimulus strength is increased Force of contraction precisely controlled by MMUS Multiple Motor Unit Summation or recruitment Recruitment brings more and more motor units into play Note that as the stimulus intensity increases (Fig. 1) more and more motor units are stimulated (Fig.2) and thus the strength of muscle contraction increases (Fig. 3).

The Arrangement of Motor Units in a Skeletal Muscle

Figure 10.17

Force of Muscle Contraction

The force of contraction is affected by:
The relative size of the muscle
Larger muscles have larger and more muscle fibers Larger fibers can generate more force than smaller fibers More muscle fibers can generate more force than fewer fibers

The number of muscle fibers contracting

Greater numbers of motor units generate more force than smaller numbers of motor units

Degree of muscle stretch

Muscles contract strongest when muscle fibers are 80-120% of their normal resting length

Force of Muscle Contraction

Figure 9.20 (a)

Isometric and Isotonic Contractions

Isometric muscle contraction

Tension (force) does not exceed resistance (load) important in postural muscle function

Isotonic muscle contraction

Tension exceeds resistance
tension while shortening = concentric tension while lengthening = eccentric

Muscle contraction requires large amounts of energy

ATP provides immediate energy for muscle contractions. Produced from three sources
Creatine phosphate (CP)
Most rapid method of ATP generation Only 1 ATP per CP used

Aerobic respiration
Requires oxygen and breaks down glucose to produce ATP, carbon dioxide and water Most efficient method Generates 36 ATP per glucose molecule

Anaerobic respiration (Glycolysis)

Occurs in absence of oxygen Results in breakdown of glucose to yield ATP and lactic acid

Muscle Metabolism: Energy for Contraction

Figure 9.18

Short-Term Energy Needs

Creatine phosphate system creatine kinase ADP + CP C + ATP CP levels quickly exhausted during intense contractions Able to sustain maximum contractions for 8-10 seconds CP (creatine phosphate) regenerated during resting conditions (ATP + C CP + ADP) Glycogen-lactic acid system takes over produces ATP for 30-40 seconds of maximum activity playing basketball or running around baseball diamonds muscles obtain glucose from blood and stored glycogen

Long-Term Energy Needs

Aerobic respiration needed for prolonged exercise
Produces 36 ATPs/glucose molecule

After 40 seconds of exercise, respiratory and cardiovascular systems must deliver enough oxygen for aerobic respiration
oxygen consumption rate increases for first 3-4 minutes and then levels off to a steady state

Limits are set by depletion of glycogen and blood glucose, loss of fluid and electrolytes

Fatigue
Progressive weakness from use
ATP synthesis declines as glycogen is consumed Sodium-potassium pumps fail to maintain membrane potential and excitability Lactic acid buildup inhibits enzyme function Accumulation of extracellular K+ hyperpolarizes the cell Motor nerve fibers use up their acetylcholine

Oxygen Debt
Vigorous exercise causes dramatic changes in muscle chemistry For a muscle to return to a resting state:
Oxygen reserves must be replenished Lactic acid must be converted to pyruvic acid Glycogen stores must be replaced ATP and CP reserves must be resynthesized

Oxygen debt the extra amount of O2 needed for the above restorative processes

Recovery period
Begins immediately after activity ends Oxygen debt (excess post-exercise oxygen consumption)
Amount of oxygen required during resting period to restore muscle to normal conditions

Endurance
Ability to maintain high-intensity exercise for >5 minutes: determined by
VO2 max or Maximal oxygen uptake
maximum capacity of an individual's body to transport and utilize oxygen during incremental exercise Measured as the millilitres of oxygen per kilogram of bodyweight per minute (ml/kg/min) average young untrained male will have a VO2 max of approximately 3.5 litres/minute and 45 ml/kg/min
Miguel Indurain is reported to have had a VO2 max of 88.0 at his peak

average young untrained female will score a VO2 max of approximately 2.0 litres/minute and 38 ml/kg/min To calculate yours go to:
http://health.drgily.com/walking-test-peak-aerobic-capacity.php

Nutrient availability

Types of Skeletal Muscle Fibers

Skeletal muscle cells are specialized into 2 main types in humans and primates Specialization allows either
High work rates (power output) Long duration contractions

2 cell types are differentiated on whether gene for a slow or fast myosin isoenzyme is expressed in the cell
i.e. cell will have a moderate or a high ATPase activity or recycling time

Muscle Performance:
Types of skeletal muscle fibers
Slow-twitch or high-oxidative Contract more slowly Moderate power output Consume ATP at moderate rates High capillary density (rich blood supply) More mitochondria Smaller in diameter
Minimize diffusion distances for oxygen and nutrients

Large amount of myoglobin. More fatigue-resistant than fast-twitch

If blood supply adequate, great endurance

Postural muscles, more in lower than upper limbs. Dark meat of chicken.

Slow and Fast Fibers

Fast-twitch or low-oxidative Respond rapidly to nervous stimulation Maximal ATP consumption can be met only by glycolysis Contain myosin that can break down ATP more rapidly than that in slow-twitch fibers Less blood supply (paler in color) Fewer and smaller mitochondria than slow-twitch Fatigue rapidly as glycogen is depleted Lower limbs in sprinter, upper limbs of most people White meat in chicken. Distribution of fast-twitch and slow-twitch Most muscles have both but varies for each muscle

Strength and Conditioning

Strength of contraction
muscle size and fascicle arrangement
3 or 4 kg / cm2 of cross-sectional area

size of motor units and motor unit recruitment length of muscle at start of contraction

Resistance training (weight lifting)

stimulates cell enlargement due to synthesis of more myofilaments

Endurance training (aerobic exercise)

produces an increase in mitochondria, glycogen and density of capillaries

Atrophy: decrease in muscle size

Smooth Muscle
Composed of spindle-shaped fibers with a diameter of 2-10 m and lengths of several hundred m Often organized into two layers (longitudinal and circular) of closely apposed fibers Found in walls of hollow organs (except the heart)

Microscopic Anatomy of Smooth Muscle

SR is less developed than in skeletal muscle and lacks a specific pattern T tubules are absent There is no troponin complex Plasma membranes have pouchlike infoldings called caveoli
Ca2+ is sequestered in the extracellular space near the caveoli, allowing rapid influx when channels are opened

There are no visible striations and no sarcomeres Thin and thick filaments are present

Proportion and Organization of Myofilaments in Smooth Muscle

Thick filaments have heads along their entire length There is no troponin complex Thick and thin filaments are arranged diagonally, causing smooth muscle to contract in a corkscrew manner Noncontractile intermediate filament bundles attach to dense bodies (analogous to Z discs) at regular intervals

Proportion and Organization of Myofilaments in Smooth Muscle

Figure 9.26

Stimulation of Smooth Muscle

Involuntary and contracts without nerve stimulation
Hormones, CO2, low pH, stretch, O2 deficiency

Autonomic nerve fibers have beadlike swellings called varicosities containing synaptic vesicles
stimulates multiple myocytes at diffuse junctions

Innervation of Smooth Muscle

Figure 9.25

Contraction of Smooth Muscle

Whole sheets of smooth muscle exhibit slow, synchronized contraction They contract in unison, reflecting their electrical coupling with gap junctions Action potentials are transmitted from cell to cell Some smooth muscle cells:
Act as pacemakers and set the contractile pace for whole sheets of muscle Are self-excitatory and depolarize without external stimuli

Contraction Mechanism
Actin and myosin interact according to the sliding filament mechanism The final trigger for contractions is a rise in intracellular Ca2+ Ca2+ is released from the SR and from the extracellular space Ca2+ interacts with calmodulin and myosin light chain kinase to activate myosin

Role of Calcium Ion

Ca2+ binds to calmodulin and activates it Activated calmodulin activates the kinase enzyme Activated kinase transfers phosphate from ATP to myosin cross bridges Phosphorylated cross bridges interact with actin to produce shortening Smooth muscle relaxes when intracellular Ca2+ levels drop See Fig 9.24 in text

Response to Stretch
Smooth muscle exhibits a phenomenon called stress-relaxation response in which:
Smooth muscle responds to stretch only briefly, and then adapts to its new length The new length, however, retains its ability to contract This enables organs such as the stomach and bladder to temporarily store contents

Hyperplasia
Certain smooth muscles can divide and increase their numbers by undergoing hyperplasia This is shown by estrogens effect on the uterus
At puberty, estrogen stimulates the synthesis of more smooth muscle, causing the uterus to grow to adult size During pregnancy, estrogen stimulates uterine growth to accommodate the increasing size of the growing fetus

Types of Smooth Muscle: Single Unit

The cells of single-unit smooth muscle, commonly called visceral muscle:
Contract rhythmically as a unit (as one) Are electrically coupled to one another via gap junctions Often exhibit spontaneous action potentials Are arranged in opposing sheets and exhibit stress-relaxation response

Types of Smooth Muscle: Multiunit

Multiunit smooth muscles are found:
In large airways to the lungs In large arteries In arrector pili muscles Attached to hair follicles In the internal eye muscles

Multi-unit smooth muscle cells are innervated by more than one motor neuron