CONTRACTION OF SKELETAL MUSCLE

contract only under the control of the nervous system Communication between the nervous system and a skeletal muscle fiber occurs at neuromuscular junction (NMJ), or myoneural junction

The Neuromuscular Junction (NMJ) Each skeletal muscle fiber is controlled by a neuron at a single NMJ A single axon branches and ends at an expanded synaptic terminal The cytoplasm of the synaptic terminal contains mitochondria and vesicles filled with molecules of acetylcholine (ACh). ACh trigger the contraction of the muscle fiber.

A narrow space, the synaptic cleft, separates the synaptic terminal of the neuron from the opposing sarcolemmal surface.

This surface (motor end plate), contains membrane receptors that bind ACh.
The synaptic cleft and sarcolemma also contain the enzyme acetylcholinesterase (AChE), or cholinesterase, which breaks down ACh.

When a neuron stimulates a muscle fiber, the process occurs in a series of steps:

STEP 1: The arrival of an action potential.

The stimulus for ACh release is the arrival of an electrical impulse at the synaptic terminal.

STEP 2: The release of ACh.

When that impulse reaches the synaptic terminal, permeability changes in the membrane trigger the exocytosis of ACh into the synaptic cleft. This exocytosis is accomplished when vesicles in the synaptic terminal fuse with the membrane of the neuron.

STEP 3: ACh binding at the motor end plate.

ACh molecules diffuse across the synaptic cleft and bind to ACh receptors on the motor end plate's surface. When ACh binding occurs, it changes the permeability of the sarcolemma to sodium ions. When the membrane permeability to sodium increases, sodium ions rush into the sarcoplasm. This influx continues until AChE removes the ACh from the receptors.

STEP 4: Appearance of an action potential in the sarcolemma.

The sudden inrush of sodium ions results in the generation of an action potential in the sarcolemma at the edges of the motor end plate. This electrical impulse sweeps across the entire membrane surface and travels along each of the transverse tubules. The arrival of an action potential at the synaptic terminal thus leads to the appearance of an action potential in the sarcolemma.

STEP 5:

Return to the initial state

Even before the action potential has spread across the entire membrane, the ACh has been broken down by AChE. Some of the breakdown products will be absorbed by the synaptic terminal and used to resynthesize ACh for subsequent release. This sequence of events can now be repeated, should another action potential arrive at the synaptic terminal.

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(1)

(2)

(3)

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Bacteria, Spiders, Snakes & U

What do the bacteria {Clostridium botulinum}, black widow spiders, cobras and humans have in common??????

They all produce

toxins

[ attack the chemical synaptic transmission at NMJ]

Botulism is caused by the neuro- toxin botulin, which is produced by the growth of C. botulinum in improperly canned foods. "Botulism comes from the Latin word for "sausage' because of the early association of the disease with poorly preserved meat Botulin is a very potent blocker of neuromuscular transmission;

As few as 10 molecules of the toxin are enough to inhibit a cholinergic synapse.

It is believed that botulin interferes with the mobilization of transmitter by Ca2+ and thus inhibits the release of ACh at the NMJ

Black widow spider venom also exerts its deadly effects by affecting transmitter release. The venom first increases, and then eliminates, ACh release at the neuromuscular junction

The bite of the cobra also results in the blockade of neuromuscular transmission in its victim.

The active compound in the snake's venom, called cobratoxin, is a peptide molecule that binds tightly to the postsynaptic nicotinic receptors and prevents their activation by ACh.

Humans have synthesised a large number of chemicals that poison synaptic transmission at the neuromuscular junction. Originally motivated by the search for chemical warfare agents, this effort led to the development of a new class of compounds called organophosphates. These are irreversible inhibitors of AChE, and by preventing the degradation of ACh, they probably kill their victims by causing a desensitisation of ACh receptors. The organophosphates used as insecticides, like parathion, are toxic to humans only in high doses.

Myasthenia gravis
Myasthenia gravis is an autoimmune disease. The name is derived from the Greek for 'severe muscle weakness.

The disorder is characterised by weakness and fatigability of voluntary muscles, typically including the muscles of facial expression, and it can be fatal if respiration is compromised.

The immune systems generate antibodies against nicotinic ACh receptors. The antibodies bind to the receptors, interfering with the normal actions of ACh at the neuromuscular junctions. In addition, the binding of antibodies to the receptors leads to secondary, degenerative changes in the structure of the NMJs that also make transmission less efficient

MUSCLE MECHANICS
Tension Production The amount of tension produced in the skeletal muscle as a whole is determined by (1) the frequency of stimulation (2) the number of muscle fibers stimulated.

The Frequency of Muscle Stimulation - A twitch is a single stimulus-contraction-relaxation sequence in a muscle fiber. - Twitches vary in duration. Eg. eye muscle fiber - 7.5 msec calf muscle - 100 msec..

A single twitch can be divided into

Contraction phase
Relaxation phase

LATENT PERIOD

The latent period Begins at stimulation and typically lasts about 2 msec. Over this period, the action potential sweeps across the sarcolemma, and Ca2+ are released by the sarcoplasmic reticulum. The muscle fiber does not produce tension because the contraction cycle has yet to begin. The contraction phase
tension rises to a peak Ca2+ bind to thin filaments. the contraction phase ends roughly 15 msec after stimulation

The relaxation phase

Continues for about another 25 msec. Ca2+ levels are falling.

Motor Units and Tension Production Contraction of muscle fiber (during movements) produces tension. The total force (tension) exerted depends on how many muscle fibers are activated. All the muscle fibers controlled by a single motor neurone called a motor unit. specific movement - specific groups of motor neurones stimulated. The amount of tension depends on how many motor unit are then recruited; >> motor units recruited - stronger the contraction.

The size of a motor unit is an indication of how fine the control of movement produced. Eg. muscles of the eye (precise control) a motor neuron control 4-6 muscle fibers. leg muscles (less precise) - a single motor neuron may control 1000-2000 muscle fibers

Some of the motor units within any particular muscle are always active, even when the entire muscle is not contracting. Their contractions do not produce enough tension to cause movement, but they do tense and firm the muscle.

This resting tension in a skeletal muscle is called muscle tone.

A muscle with little muscle tone appears limp and flaccid/soft, whereas one with moderate muscle tone is quite FIRM

& SOLID.

Resting muscle tone stabilizes the position of bones and joints.

eg. balance and posture, enough motor units are stimulated to produce the tension needed to maintain body position

ENERGY SOURCES FOR CONTRACTION

A single muscle fiber contain ~ 15 billion thick filaments. When actively contracting, EACH thick filament breaks down ~ 2500 ATPs/sec Even a small skeletal muscle contains thousands of muscle fibers, the ATP demands of a contracting skeletal muscle are enormous.

the demand for ATP in a contracting muscle fiber is so high

A resting muscle fiber contains only enough ATP and other high-energy compounds to sustain a contraction until additional ATP can be generated. During contraction, the muscle fiber will generate ATP at the same rate as it is used.

ATP and Creatine Phosphate (CP) Reserves At rest, a skeletal muscle fiber produces more ATP than it needs. Under these conditions, ATP transfers energy to creatine to form another highenergy compound, CP, or phosphorylcreatine:

ATP

muscle relaxed

Creatine

creatine phosphokinase (CPK)

ADP
** [CPK]blood serious muscle damage **

Creatine phosphate

During a contraction, each myosin cross-bridge breaks down ATP, producing ADP and a phosphate group. The energy stored in creatine phosphate is then used to "recharge" ADP, converting it back to ATP through the reverse reaction:

Creatine
creatine phosphokinase

ATP

Creatine phosphate

ADP Contracting muscle

Energy for muscle contraction

A resting skeletal muscle fiber contains ~ 6X as much CP as ATP.

When a muscle fiber undergoing a sustained contraction, these energy reserves are exhausted in only about 17 sec.

the muscle fiber must then rely on other mechanisms to convert ADP to ATP

Aerobic metabolism [ in mitochondria; Other mechanisms

Krebs cycle]

Glycolysis [in cytoplasm] (anaerobic)

Anaerobic metabolism Aerobic metabolism

Produce 17 ATPs/molecule fed/cycle

produce 38 ATPs / glucose molecule

{2 ATP in glycolysis + 2 pyruvic acid in aerobic metabolism (36ATP)}

Sources of Energy Stored in a Typical Muscle Fiber

Energy Stored as

Utilised through

Initial Quantity

Number of Twitches Supported by Each Energy Source Alone 10 70 670 12,000

Duration of Contraction Supported by Each Energy Source Alone

ATP CP Glycogen

ATP ADP + P ADP + CP ATP + C Glycolysis (anaerobic) Aerobic metabolism

3 mmol 20 mmol 100 mmol

2 sec 15 sec 130 sec 2400 sec (40 min)

Anaerobic energy production has its drawbacks:

When glycolysis produces pyruvic acid faster than it can be utilised by the mitochondria, pyruvic acid levels rise in the sarcoplasm. Under these conditions, the pyruvic acid is converted to LACTIC ACID.

lactic acid -

lower the intracellular pH. Changes in pH will alter the functional characteristics of key enzymes. The muscle fiber will then become unable to continue contracting

Muscle Fatigue A skeletal muscle is considered fatigued when it can no longer contract, despite continued neural stimulation. Can be due to : exhaustion of ATP and CP reserves

drop in pH {buildup of lactic acid}

interruption in blood supply/lack of neurotransmitter (rare)

Muscle Recovery

When a muscle fiber contracts:Energy reserves consumed

Heat released
lactic acid generated

In the recovery period, conditions inside the muscle fibers gradually returned to normal, preexertion levels. It may take several hours to a week

During recovery period, the bodys O2 demand increases. The extra O2 is used by mitochondria in;

HEPATOCYTES ATP is required for conversion of lactic acid to glucose

MUSCLE FIBERS
ATP is needed to restore ATP & glycogen reserves

The additional O2 required during recovery period is called the oxygen debt. How to pay????

the rate & depth of breathing