Muscle

Biological machine which converts chemical energy, ATP, into work.

Muscle

25-30% efficient and the rest of the energy is lost as heat.

Human muscle is...

power to weight ratio and exceeds that of any man-made machine.

Muscle has a high...

Proteins that convert the energy stored in ATP into a sliding of proteins filaments and hence muscle shortening. They are also found in white blood cells.

Contractile Proteins

Muscles attached to the skeleton which moves the bones.

Skeletal Muscle

Surrounds the hollow organs of the body, e.g. the gut.

Smooth Muscle

The muscles of the heart.

Cardiac Muscle

striated.

Skeletal and cardiac muscles are...

involuntary.

Cardiac muscle and smooth muscles are...

The plasma membrane of a muscle cell.

Sarcolemma

The cytoplasm of the muscle cell.

Sarcoplasm

The endoplasmic reticulum of a muscle cell.

Sarcoplasmic Reticulum

Movement, manipulation of external objects, propulsion of contents through hollow organs, and emptying of contents to the external environment.

Functions of Muscle

The contractile or functional unit of muscle.

Sarcomere

A large muscle is made of many single fibres of smaller subunits called myofibrils, and these fibres are single muscle cells. Each fibre is a long, cylindrical cell 1-120 milimetres long and are about 10-100 micrometres in diameter. Each fibre ends in tendons made mostly of collagen.

Skeletal Muscle Structure

Whole muscle (organ) --> muscle fibre (cell) --> myofibril (specialized intracellular structure) --> thick and thin filaments (cytoskeletal elements) --> myosin and actin (protein molecules)

Skeletal Muscle Breakdown

each cell must be stimulated by a process of a motor neuron.

In order for skeletal muscle to contract...

Motor neuron, its axon, and all the muscle fibres it activates. Refers to all the muscle fibres that a single neuron motor nerve innervates. It is the functional unit of the motor system and represents the smallest increment in force that can be generated.

Motor Unit

One nerve which controls hundreds of muscle fibres.

Gross Movements

One nerve controls 5-6 muscle fibres.

Fine Movements

Light region in the middle of the A band.

H Zone (Microscopic Muscle)

Dark with a slightly lighter region in the centre.

A Band (Microscopic Muscle)

Transverse line in the middle of the H zone.

M Line (Microscopic Muscle)

Light regions.

I Band (Microscopic Muscle)

Narrow dark line in the middle of the I band.

Z Line (disk, Microscopic Muscle)

sarcomere, 2-3 micrometres.

The distance from Z line to Z line is a...

identical

All sarcomeres in a muscle fibre are...

Myosin

Thick Filaments A Band Protein

Actin

Thin Filaments I Band Protein

actin, myosin, troponin, tropomyosin, ATP, traces of magnesium ions, and greater than 10^-7 M calcium ions.

Muscle contraction requires:

Composed of actin (double stranded alpha helical polymer of actin) and is tethered at one end of the Z disk. F actin is associated with two actin binding proteins, tropomyosin and troponin. Contain nebulin which helps to anchor the filaments to the Z disk.

Thin Filaments

Two identical alpha helices which shadow the actin double helix.

Tropomyosin

Heterotrimer that comes in three important forms: TnT (binds tropomyosin), TnC (binds calcium ions - 4 binding sites in skeletal muscle and 3 binding sites in cardiac muscle), and TnI (binds actin monomers).

Troponin

Polymers of myosin II. Myosin is a double trimer consisting of two intertwined heavy chains (rod, hinge, and head regions), two regulatory light chains, and two alkali light chains.

Thick Filaments

Are cross bridges which contain binding sites for actin and sites for binding and hydrolyzing ATP.

Heads of Myosin

Large elastic protein which anchors the thick myosin filament to the Z disk and provides some elastic recoil.

Titin

Hold the thick filament in precise alignment at the M line.

C Proteins and Myomesin

Attach the actin filament to the Z disk.

Alpha-Actinin

Helps to anchor actin the the Z disk.

Nebulin

Upon contraction: A band remains constant, I band shortens, Z lines move closer together, H zone gets smaller or disappears. Actin filaments must slide between the myosin, i.e. the sarcomere changes length.

Sliding Filament Theory

H zone, cross bridges, myosin heads.

During contraction the actin filaments are pulled towards the _____ by _______ or _______.

Describes the calcium-dependent interaction of actin and myosin during muscle contraction.

Cross-Bridge Cycle

contractile proteins convert energy of ATP hydrolysis into mechanical energy. ATP binds the myosin head and ATP is hydrolysed, the myosin head binds to a new position on the actin filament, the release of Pi triggers the power stroke, and ADP is released from the myosin head.

During the cross-bridge cycle...

reduces affinity of myosin for actin and the myosin head is released from the actin.

ATP binding to the myosin head...

runs ATP into ADP and Pi and the myosin head pivots into the cocked position.

ATP hydrolysis...

increases the affinity of the myosin complex for actin.

The myosin head binding a new position...

triggers the power stroke; there is a conformational change in the myosin head about the hinge and actin is pulled about 11 nM along the myosin filament.

Release of the Pi...

rigor complex

The actin-myosin complex is know as the...

cross-bridges are inactive and the muscle is relaxed.

When [Ca2+] < 10^-7 M...

the muscle contracts.

When [Ca2+] > 10^-7 M...

internal, calcium ions, contractile proteins.

The action potential increases the ______ concentration of _____ near the _________.

myosin complex, tropomyosin

At low [Ca2+], the _________ can not bind to actin because ________ is in the way.

TnC

_____ in skeletal muscle has four binding sites for calcium ions, 2 of which are high affinity and 2 of which are low affinity.

four calcium ions bind to the TnC of troponin complex. TnI and TnT undergo a conformational change which removes the steric interference by moving deeper into the groove of the actin filament.

When calcium ion concentration is high...

increasing [Ca2+] , decreasing [Ca2+]

Contraction may be turned on by ________ near the myofibrils and off by ___________ near the myofibrils.

sarcoplasmic reticulum, transverse tubules

In skeletal muscle, the __________ stores calcium ions and removes it to allow relaxation and the _________ synchronizes the release of calcium ions.

surrounds the myofibrils and has Ca2+ release channels located near the transverse tubules (ryanodine receptors); it stores Ca2+ in the terminal cisternae and has Ca2+ pumps which remove it from the cytoplasm (SERCA 1 and SERCA 2A).

The sarcoplasmic reticulum...

speeds up, Ca2+

The sarcoplasmic reticulum _________ contraction in skeletal muscle because _______ has shorter distances to diffuse.

Duct system that synchronizes the release of Ca2+ from the terminal cisternae of the sarcoplasmic reticulum. They carry nutrients, ions, and action potentials deep into the cell.

Transverse Tubules

extensions of the surface membrane and enter at the junctions of the A and I bands. They are coupled with ryanodine receptors on the SR via the DHP receptors.

Transverse tubules are....

Rudimentary invaginations in smooth muscle which contacts the SR.

Caveolae

DHP receptor

L-Type Ca2+ Channel

Ryanodine receptor

Ca2+ Release Channel

Action potential at the surface membrane --> activates L-type Ca2+ channels on t-tubule membrane which induces Ca2+ release from the SR via the ryanodine receptors --> Ca2+ binds troponin --> conformational change in troponin moves tropomyosin out of the way --> actin binding, Pi released, contraction --> Ca2+ < 10^-7 M in cytoplasm because of SERCA 1 action --> troponin goes back to original shape, tropomyosin slips back and blocks actin

Muscle Contraction Summary

Na+/Ca2+ exchanger NCX (skeletal/cardiac/smooth), surface Ca2+ pump PMCA (skeletal/cardiac/smooth), sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA; skeletal/cardiac/smooth), calsequestrin (skeletal/cardiac) or calreticulin (smooth)

Mechanism of Cytoplasmic Calcium Removal

Creatine phosphate: CrP + ADP

Supplemental Source of Muscle Energy

White muscle, glucose ---> 2 ATP + lactate

Severe Exercise Conditions...

The length of the muscle is held constant and the force produced is measured (no shortening of sarcomeres). Tendons are elastic so there is a small amount of shortening. Pushing against immoveable loads is isometric.

Isometric (Constant Length) Contraction

The load (weight) on the muscle is held constant and the length change is measured. Body movements are isotonic.

Isotonic (Constant Tension) Contraction

Transient contraction phase followed by a relaxation phase (response to a single action potential).

Twitch

Initiating a second action potential before the first contraction has completely relaxed. There is an increase in muscle tension or shortening in response to a rapid, repetitive stimulation relative to a single twitch. If the frequency is high enough tetanus occurs.

Summation

free Ca2+ remains high, allowing maximal force to be developed. The Ca2+ pumps in the sarcoplasmic reticulum can not catch up and cause relaxation.

Tetanus occurs because...

twitch speed.

Fusion frequency depends on....

size, smallest, largest

Motor units during voluntary contraction are activated on the basis of _____. ____ first, _____ last.

Force a muscle develops depends on the actin myosin overlap. As overlap decreases so does force. At short lengths, actins interfere.

Active Length-Tension Relationship

Resistant to fatigue, red in colour (myoglobin), oxidative, MHC-I, SERCA2a, RyR1, fast calsequestrin, troponin C1.

Slow Twitch Type I Fibres

Resistant to fatigue, red in colour (myoglobin), oxidative, MHC-IIa, SERCA1, RyR1, fast calsequestrin, troponin C2.

Fast Twitch Type IIa Fibres

Fatigable, white in colour, glycolytic, MHC-IIb, SERCA1, RyR1, fast calsequestrin, troponin C2.

Fast Twitch Type IIb Fibres

Striated, 100 micrometers long and 15 micrometers wide, connected longitudinally by intercalated disks using desmosomes and have gap junctions.

Gross Structure of Cardiac Muscle

less, 10 times larger

The cardiac muscle sarcoplasmic reticulum is _____ developed than that of skeletal muscle but the transverse tubules are _______ than those of skeletal muscle.

receptors for circulating transmitters.

An important characteristic of cardiac muscle is that is expresses...

absolute requirement, t-tubules, sarcoplasmic reticulum

Ca2+ influx through the L-type channels is an ______ for cardiac contraction. The _______ have L-type channels and the __________ has calcium ion release channels.

dyad (SR cisterna/t-tubules), triad (SR cisterna/t-tubules/SR cisterna)

Cardiac muscle is a ______ whereas skeletal muscle is a _____.

calcium-induced Ca2+ release (CICR)

The excitation-coupling mechanism in cardiac muscle is called...

(1) Na+/Ca2+ exchanger in the plasma membrane (NCX, 10%), (2) Ca2+-ATPase in the SR (SERCA2A, 90%)

Cardiac Muscle Relaxation Mechanisms

Small spindle shaped cells, no visible striations under microscope, actin and myosin are present but the relationship is less highly organized, actin filaments are oriented mainly parallel or oblique to the long axis of the cell, multiple actin filaments join at dense bodies which are found immediately beneath the cell membrane and within the cell interior, thick filaments are interspersed among the thin filaments.

Gross Structure of Smooth Muscle

troponin

Smooth muscle does not have...

actin, myosin, tropomyosin, calmodulin, myosin light kinase, and myosin light chain phosphatase.

Smooth muscle contains...

terminating contraction.

Myosin light chain phosphatase is important for...

Cells are innervated by the autonomic nervous system, the neuron makes multiple contacts with the cell and at each contact point the neuron expands to form a varicosity, there is no defined motor end plate, receptors are widely spread across the post-synaptic membrane, few gap junctions, each muscle cell acts independently of each other.

Multiunit Smooth Muscle

Iris and ciliary body of the eye, piloerector muscles of the skin, some blood vessels.

Multiunit Smooth Muscle Examples

Cells are innervated by the autonomic nervous system (varicosities), cells are electrically coupled via gap junctions which allows contraction as a single unit or in sheets.

Unitary Smooth Muscle

GI tract, uterus, bladder, some blood vessels.

Unitary Smooth Muscle Examples

Slow waves --> voltage-gated Ca2+ channels open, action potential spike, Ca2+ influx thus rise in internal Ca2+ concentration, open Ca2+ dependent K+ channels, slow hyperpolarization, voltage-gated Ca2+ channels close and internal Ca2+ concentration decreases, Ca2+ dependent K+ channels close, repeat.

Electrical Activity of Smooth Muscle

Ca2+ dependent phosphorylation of myosin (smooth muscle myosin heads can interact with actin only when the myosin light chain is phosphorylated), an increase in Ca2+ concentration initiates a chain of events that increase the ATPase activity of myosin (2 Ca2+ bind to calmodulin, Ca2+-calmodulin activates myosin light chain kinase, MLCK phosphorylates the regulatory light chain on the myosin II head which increases ATPase activity and allows it to bind to actin).

Cross Bridge Cycling in Smooth Muscle

myosin light chain kinase (MLCK) which phosphorylates regulatory myosin head to increase ATPase activity which is essential.

In smooth muscle cross-bridging, calcium activates...

reduction of [Ca2+], dephosphorylation, myosin light chain phosphatase.

Relaxation of smooth muscle requires not only a ________ but also the _______ of the myosin light chain by ________.

contraction, relaxation

Phosphorylation is associated with _____ and dephosphorylation is associated with ______.

Ca2+-dependent (means while the SR is removing calcium from the cytosol the phosphatase can still be active, it can work even as calcium levels drop).

Myosin light chain phosphatase is not _____.

L-type Ca2+ channels

Smooth Muscle Voltage-Dependent Channels