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BIOL 2401

Muscles & Physiology I

Collin County Community College

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Skeletal muscle •  attached primarily to bone •  striated •  voluntary

Cardiac muscle •  heart muscle tissue •  striated but involuntary •  includes a pacemaker system that causes the heart to beat

Smooth Muscle •  located in the walls of hallow internal structures •  non-striated (therefore appears as "smooth" ) •  involuntary

TYPES OF MUSCLE

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TYPES OF MUSCLE

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•  Produces motion •  involved in the integrated functioning and

movement of bones and joints via skeletal muscle

•  less noticeable is the motion of the heart and that of the internal organs such as gut

•  Supports soft tissues and Regulates organ volume •  Generates heat : muscle contraction generates 80-85

% of body heat

•  Stabilizes joints

•  Maintain posture

FUNCTION OF MUSCLE

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•  Excitability : ability to respond to stimuli (chemical) by producing electrical signals (current)

•  Extensibility : ability to stretch without damage to the tissue (opposing muscle is always stretched when primary muscle contracts)

•  Contractility : ability to shorten and thicken (contract), thereby producing force

•  Elasticity: ability to return to its original length and shape after being stretched

CHARACTERISTICS OF MUSCLE

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Skeletal muscles attach to bones across joints

Skeletal muscles are organized in agonistic/ antagonistic pairs.

A muscle can shorten and pull on a bone, but cannot push a bone away .

CHARACTERISTICS OF MUSCLE

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Prefix Terminology with respect to muscles.

Myo - : refers to muscle •  myo-cyte •  myo-fillament

CHARACTERISTICS OF MUSCLE

Sarco - : means flesh used in for example

•  sarcolemma •  sarcoplasma •  sarcoplamic reticulum

Cardio - : refers to the heart

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Skeletal muscles are attached to the skeleton by tendons.

A single muscle cell is called a muscle fiber.

A muscle bundle is made out of groups containing many individual muscle cells. Such groups are called fascicles.

Anatomy of Skeletal Muscle

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Bone

Perimysium

Endomysium (between individual muscle fibers)

Muscle fiber

Fascicle (wrapped by perimysium)

Epimysium

Tendon

Epimysium

Muscle fiber in middle of a fascicle

Blood vessel

Perimysium Endomysium

Fascicle (a)

(b)

Anatomy of Skeletal Muscle

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Epimysium : •  surrounds the whole muscle •  made from dense regular CT •  attaches to periosteum of bone

Perimysium •  surrounds the fascicles

Endomysium •  surrounds each muscle fiber •  made from areolar CT

Three layers of connective tissue are part of each muscle.

At the end of the muscle, the 3 C.T. tissues come together and form a tendon or an aponeuris (broad tendon sheet).

Anatomy of Skeletal Muscle

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Anatomy of Skeletal Muscle

•  Each muscle is served by one nerve, an artery, and one or more veins

•  Each skeletal muscle fiber is supplied with a nerve ending that controls contraction

•  Contracting fibers require continuous delivery of oxygen and nutrients via arteries

•  Wastes must be removed via veins

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Muscle cells originate from the fusion of embryonic cells called myoblasts. Each cell is thus a syncytium produced by fusion of embryonic cells

They are thus multinucleate are in general slender and long ( 100 um wide, sometimes 12 inches long)

Satellite cells are unfused myoblast cells that remain active in assisting the regeneration of damaged muscle fibers

Skeletal Muscle Fibers (cells)

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Skeletal Muscle Fibers (cells)

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Skeletal Muscle Fibers (cells)

•  Each muscle fiber (cell) is a long, cylindrical cell with multiple nuclei just beneath the sarcolemma

•  Fibers are 10 to 100 mm in diameter, and up to hundreds of centimeters long

•  Sarcoplasm has numerous glycosomes (glycogen containing bodies) and a unique oxygen-binding protein called myoglobin

•  Fibers contain the usual organelles such as mitochondria, sarcoplasmic reticulum and special structures called myofibrils and T tubules.

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Each skeletal muscle fascicle is typically composed of many muscle fibers (cells).

Each muscle fiber (=muscle cell) is packed with long cylindrical myofibrils.

Each myofibril in turn is made out of smaller protein based structures called myofilaments .

The myofilaments are organized into sarcomeres, which are the contractile units of a muscle cell.

Micro-Anatomy of Skeletal Muscle

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Micro-Anatomy of Skeletal Muscle

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MyoFibrils

•  Myofibrils are densely packed, rodlike contractile elements

•  They make up most of the muscle volume •  The arrangement of myofibrils within a fiber is such that a

perfectly aligned repeating series of dark bands (the A bands) and light bands (the I bands) are evident

Muscle cell

Nucleus Light I band Dark A band

Sarcolemma

Mitochondrion

Myofibril

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Myofibrils & Myofilaments

Each myofibril is made from bundles of proteins called the myofilaments.

There are two major proteins involved :

•  Actin : they form the thin filaments

•  Myosin : they form the thick filaments

These proteins within the myofibrils are the actual contractile elements of a muscle

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Sarcomeres

•  Each myofibril is made up of around 10,000 sarcomeres arranged in series (back to back)

•  The sarcomere is smallest contractile unit of a muscle •  The region of a myofibril between two successive Z discs •  Composed of myofilaments made up of the contractile

proteins actin, mysosin and other proteins.

Myo-fibril

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Sarcomeres : the unit of contraction

• Thick filaments: run the entire length of an A band • Thin filaments: run the length of the I band and

partway into the A band • Z disc: coin-shaped sheet of proteins that anchors the

thin filaments and connects myofibrils to one another • H zone: lighter midregion where filaments do not

overlap • M line: line of protein myomesin that holds adjacent

thick filaments together

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Sarcomeres : the unit of contraction

I band I band A band Sarcomere

H zone Thin (actin) filament

Thick (myosin) filament

Z disc Z disc

M line

(c) Small part of one myofibril enlarged to show the myofilaments responsible for the banding pattern. Each sarcomere extends from one Z disc to the next.

Z disc Z disc M line Sarcomere

Thin (actin) filament

Thick (myosin) filament

Elastic (titin) filaments

(d) Enlargement of one sarcomere (sectioned lengthwise). Notice the myosin heads on the thick filaments.

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The thin filament (F-actin) called actin is a polymer of G-actin molecules.

Each G-actin molecule has a binding site to which a myosin head can bind

Structure of Thin Filaments

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The binding sites on actin are covered by a tropomyosin filament.

The tropomyosin filament is attached to the actin chain by means of a Troponin complex.

Structure of Thin Filaments

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In relaxed skeletal muscle, tropomyosin blocks the myosin head (also called cross-bridge) binding site on actin.

When calcium ions bind to troponin , the troponin complex pulls tropomyosin away from the cross-bridge binding site.

This allows myosin cross-bridges to attach to actin and is at the basis of muscle contraction.

Structure of Thin Filaments

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The thick filament called myosin is actually a polymer of myosin molecules

Each has a flexible cross-bridge (head) with ATPase activity and with a binding site for actin.

Structure of Thick Filaments

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Structure of Thick Filaments

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Structure of Thick Filaments

Myosin head

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Structure of Myofibril and Sarcomere

Each thick filament is surrounded in a hexagonal pattern by 6 thin filaments.

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The cell membrane of a Skeletal muscle is called sarcolemma

It is an excitable membrane ; has similar properties as a nerve cell membrane

•  Has a resting membrane potential •  Has the ability to generate action potentials along

that membrane (what does this implicate ? )

Sarcolemma and Skeletal Muscle

IN nerve tissue, the purpose of the action potential is guide the electrical activity towards the axon terminal end-point, where it results in the release of Neurotransmitters !

The purpose of the action potential on a muscle cell is to start the process of contraction.

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Problem : SR is located within the cell and the Action Potentials run along the plasma-membrane !

T-tubules and SarcoPlasmic Reticulum

Skeletal Muscle contraction is started by the release of calcium from the internal stores, the Sarcoplasmic Reticulum (SR)

S.R Contains [Ca2+]

- - - - - - + + + +

Motor neuron

Act. Pot.

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T-tubules and Sarcolemma

The action potential has to be guided to the inside of the cell to ‘reach out and touch’ the SR .

This is accomplished by narrow membrane pits, tubular extension of the plasma membrane that extend deep within the sarcoplasma. These are called the T-tubules !

S.R Contains [Ca2+]

- - - - - - + + + + ++++

- - - - - -

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•  T-tubules dip into the cell at the Z-discs •  Smooth endoplasmic reticulum of a muscle cell =

•  sarcoplasmic reticulum •  encircles the contractile elements of the cell with

interconnecting tubules that run longitudinally

•  Interconnecting sacs of the SR run on either side of the T-tubules = terminal cisternae or end sacs

•  Combination of T-tubules and a pair of surrounding terminal cisternes = Triad system

•  Calcium is released from the SR via special Calcium-release channels that respond to a voltage change  

T-tubules and SarcoPlasmic Reticulum

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T-tubules and Sarcolemma

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T-tubules and Sarcolemma

Myofibril

Myofibrils

Triad:

Tubules of the SR

Sarcolemma

Sarcolemma

Mitochondria

I band I band A band H zone Z disc Z disc

Part of a skeletal muscle fiber (cell)

• T tubule • Terminal

cisternae of the SR (2)

M line

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Contraction of a muscle fiber

•  Occurs when the myosin heads latch on to the actin filament

Called the sliding filament theory

•  This sliding results in the sarcomere to shorten without altering the length of actin or myosin filaments

•  This causes the actin filaments to slide inwards and to pull the z-line towards each other

•  The cross bridges then pull forward

Aspect of Contraction

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Aspect of Contraction

During Contraction and shortening the myofilaments ( thick and thin filaments) do not shorten ! THEY SLIDE OVER EACH OTHER . •  The sarcomere shortens •  The A bind remains the same size - The I band shortens    

A band I band

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Aspect of Contraction

1.  Activation = neural stimulation via motor neuron and release of N.T. at a neuromuscular junction

2.  Excitation-contraction coupling: –  Generation and propagation of an action potential along

the sarcolemma –  Final trigger: a brief rise in intracellular Ca2+ levels via

release from the Sarcoplasmic Reticulum

Requirements for Skeletal Muscle Contraction

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NeuroMuscular Junction

•  Area where somatic motor neuron (axon) and skeletal muscle cells make contact

•  The motor end plate is the surface of the muscle cell where the synapse occurs.

•  As a rule, each muscle fiber (cell) has only one NMJ but one motor neuron can activate many cells via collateral branches.

•  Synapse is between the motor neuron axon on one side and the motor endplate on the other side

•  ACh is the neurotransmitter and the motor endplate carries ACh receptors

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Events at NMJ

•  Release of ACh is triggered by an AP and results in opening of voltage gated Ca-channels in the axon terminal of the motor neuron.

•  Binding of ACh at the motor endplate opens up chemically gated Na-channels (nicotinic ACh receptor)

•  This triggers a local de-polarization (graded potential) that reaches outside of the NMJ area

•  Outside the NMJ, voltage gated Na-channels respond to this graded depolarization and open, triggering an Action

potential along the sarcolemma

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NeuroMuscular Junction

Nucleus

Action potential (AP)

Myelinated axon of motor neuron

Axon terminal of neuromuscular junction

Sarcolemma of the muscle fiber

Ca2+ Ca2+

Axon terminal of motor neuron

Synaptic vesicle containing ACh Mitochondrion

Fusing synaptic vesicles

1 Action potential arrives at axon terminal of motor neuron.

2 Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal.

3 ACh relesed into synaptic cleft area Synaptic cleft

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Na+

Na+

Open Na+ Channel

Closed K+ Channel

K+

Na+ K+ Action potential + + + + + + + + + + + +

Axon terminal

Synaptic cleft

ACh

ACh

Sarcoplasm of muscle fiber

K+

ACh binds to and opens nicotinic Na-channel

local depolarization: generation of the end plate graded potential on the sarcolemma

W a v e o f d e

p o l a r i z

a t i o

NeuroMuscular Junction

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Na+ channels close, K+ channels open

K+ channels close

Repolarization due to K+ exit

Threshold

Na+ channels open

Depolarization due to Na+ entry

Sarcolemma Action Potential

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Excitation-Contraction (E-C) Coupling

•  Excitation-Contraction coupling is the sequence of events by which transmission of an AP along the sarcolemma leads to sliding of the myofilaments

•  There is an initial latent period: this is the time between AP initiation and the beginning of contraction – Time when the molecular/cellular aspects of E-C

coupling events occur

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Steps in E-C Coupling:

Terminal cisterna of SR

Voltage-sensitive tubule protein T tubule

Ca2+ release channel

Ca2+

Sarcolemma

Action potential is propagated along the sarcolemma and down the T tubules.

Calcium ions are released.

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Steps in (E-C) Coupling

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Steps in (E-C) Coupling

Troponin Tropomyosin blocking active sites Myosin

Actin

Active sites exposed and ready for myosin binding

Ca2+

Myosin cross bridge

Calcium binds to troponin and removes the blocking action of tropomyosin.

Contraction begins

The aftermath

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Muscle fiber Contraction

•  Starts when calcium binds to troponin, allowing tropomyosin to shift out of the way and un-block the myosin head binding sites.

•  ATP will now provide the energy so that the myosin heads pull back and forth on the actin strands, creating the sliding of thin over thick filaments

•  The pulling of myosin heads on actin occurs via cross bridge formations

•  The direction of the pull is towards the middle of each sarcomere

•  Each mysoin head will cycle back and forth like a rower in a rowboat as long as calcium and ATP is available in the cytoplasm

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Actin

Cross bridge formation.

Myosin cross bridge

Thick filament

ADP

Pi

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The power (working) stroke.

ADP

Pi

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ADP

Muscle fiber Contraction: Powerstroke The powerstoke occurs when the myosin head actually pulls on actin.

It occurs when the myosin head lets go of hydrolyzed ATP ( ADP and Pi)

The binding of an ATP molecule to the myosin head, the energizing of the myosin head by splitting ATP and the release of that energy via the powerstroke, are very similar to putting an arrow into a bow and putting tension on the bowstring. The powerstroke is then similar to letting the arrow fly.

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ATP

ADP

ADP ATP hydrolysis

ADP

ATP

Pi

Pi Myosin head (high-energy configuration)

Myosin head attaches to the actin myofilament, forming a cross bridge.

Thin filament

As ATP is split into ADP and Pi, the myosin head is energized (cocked into the high-energy conformation).

Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released.

Myosin head (low-energy configuration)

As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches.

Thick filament

1

4 2

3

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Muscle fiber Contraction: Powerstroke •  The important aspect is that ATP needs to bind to the mysoin head

in order for the mysoin head to detach from the actin

•  The splitting of ATP into ADP and Pi provides the potential energy by snapping the head back into a potential powerstoke position. (like the pulling on the string of a bow to transfer the energy into the string as potential energy)

•  During a single contraction, about 50% of the mysoin heads are puling while 50% are re-setting themselves

•  A single sarcomere does not have to shorten much in order to get a muscle group to shorten 1 cm ( for ex: if a muscle cell has 10,000 sarcomeres one after another, how much does each need to shorten ?)

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End of a Single Contraction: Relaxation

•  a single nerve impulse needs to correlated with a single muscle contraction

•  released ACh in the synaptic cleft of the NMJ diffuses away AND is quickly destroyed by AcetylCholine-esterase.

•  this prevents continued muscle stimulation in the absence of nerve impulses.

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End of a Single Contraction: Relaxation

•  In addition, strong Ca2+ pumps operate at the SR level : from the moment Ca2+ floods the cell, they start pumping it back into the SR

•  Thus the cell only sees a brief increase in Ca2+ : when calcium vanishes, the binding sites on actin become blocked again and the contraction stops !

•  The SR also contains special proteins that bind Calcium strongly ( Calsequestrin) : This increases the holding capacity for Calcium in the SR and facilitates the re-uptake of Calcium

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Excitation-Contraction Problems

•  Duchenne’s Muscular dystrophy •  genetically inherited disease (only males affected) •  degenerative muscle weakness, paralysis and cardiac

problems •  usually die before age 20 •  Related to lack of protein dystrophin •  Protein is suspected to play a role in calcium regulation

and stability of sarcomeres

•  Myastenia Gravis •  Results from progressive loss of ACh receptors •  Due to autoimmune response attacking the receptors

•  Botulism •  Results from consumption of contaminated canned food

progressive loss of ACh receptors •  Toxin prevents release of Ach (results in paralysis)

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Excitation-Contraction Problems

•  Curare •  binds to nicotinic receptors •  it thus blocks the ACh receptor:

no muscle contraction

•  Organophosphates : •  pesticides, nerve gas •  inhibit ACh-esterase •  maintained depolarization •  maintained contraction and no relaxation

possible ( think what it will do to your diaphragm)

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Of the two important molecules for muscular contraction, ATP and Calcium , which one would be the fastest in short supply ?

ATP versus Calcium Supply

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Function of ATP

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Rigor Mortis

Following the death of an organism, cellular homeostasis and integrity breaks down

•  No circulation, no oxygen supply to tissues •  No mitochondrial activities, no ATP production •  Calcium leaks into the cell and cannot be pumped

out •  Binds to troponin ; tropomyosin shifts out of

position •  Myosin binds to actin •  But there is no ATP for the power stroke or to

release myosin from actin •  Muscles become “locked “ in place at the thin-

thick filament level