Excitation Contraction Coupling

Question 1

How is the neuronal action potential propagated to the muscle? Describe what is happening in the neuron.

Answer 1

The AP propagates down the neuron to the presynaptic terminal (terminal button) where it depolarizes it and causes voltage-gated Ca channels to open. Increase in Ca causes vesicles to fuse with the membrane and release ACh into the synaptic cleft.

Question 2

How is the neuronal action potential propagated to the muscle? Describe what is happening in the synaptic cleft and the muscle.

Answer 2

ACh binds to ACh receptors embedded in the muscle plasma membrane at the motor endplate. ACh receptors open and allow Na to flow in (a little K out) changing the endplate potential. Voltage-gated Na channels are then activated and the AP propagates down the muscle.

Question 3

What is Myasthenia Gravis? Explain it.

Answer 3

It is an autoimmune disease where antibodies block or reduce the number of nicotinic acetylcholine receptors at the neuromuscular junction resulting in muscle fatigability.

Question 4

How is Myasthenia Gravis treated? What clinical presentation does it have?

Answer 4

Treated with edrophonium chloride which is a cholinesterase inhibitor and thus increases ACh at the neuromuscular junction. Patients will have ptosis and weakness of smile. They may feel fine in the morning but develop diplopia and speech slur later in the day. They can not resist a physician pushing their head to pull their chin off of their chest.

Question 5

Disorders of excitation contraction coupling include the following: 1-Amyotrophic lateral sclerosis. 2-Demyelinating disease (eg. Guillain-Barre Syndrome). 3-Myasthenia Gravis. 4-Malignant hyperthermia. 5-Muscular dystrophy. Explain with which part each interferes.

Answer 5

1- Motor Neuron Disease
2- Nerve disease
3- Neuromuscular Junction Disease
4- Sarcomere disease
5- Muscle disease
(pg 252)

Question 6

Can skeletal muscle contract in the absence of extracellular calcium?

Answer 6

Yes, the cycling of calcium is intracellular. The Na dependent AP triggered by ACh release at the neuromuscular junction triggers the release of Ca from an internal store inside the muscle cell.

Question 7

Describe the skeletal muscle AP and Ca release

Answer 7

The sarcolemma and T-tubules are depolarized in a Na dependent mechanisms. The depolarization of T-tubules induces a change in the structure of L-type Ca channels (embedded in the T-tubule) which in turn opens a Ca channel gate in the ryanodine receptors embedded in the sarcoplasmic reticulum releasing Ca into the sarcoplasm (cytosol)

Question 8

What composes the skeletal muscle triad?

Answer 8

1 T-tubule and 2 sarcoplasmic reticulum cisternae

Question 9

How are the terminal cisternae of SR physically attached to the T-tubules?

Answer 9

Through the direct coupling of L-type Ca channels embedded in the T-tubule membrane to the Ryanodine receptors embedded in the membrane of the SR.

Question 10

At nonmolar concentrations and micromolar concentrations what effect does the plant alkaloid Ryanodine have?

Answer 10

Nanomolar - opens

Micromolar - closes

Question 11

In which type of muscle is Ca induced Ca release most important? Describe the process

Answer 11

Cardiac muscle. The Ryanodine receptor is stimulated to open by the presence of cytoplasmic Ca. So after the L-type Ca channels open the ryanodine receptors at the triad Ca is released and causes more ryanodine receptors to release Ca. Ultimately, Ca release occurs rapidly along the entire length of the SR and not just at the triad.

Question 12

How is skeletal muscle contraction terminated?

Answer 12

By the removal of calcium from the sarcoplasm

Question 13

What is the major mechanism for Ca removal from the sarcoplasm in skeletal muscle?

Answer 13

The Sarcoplasmic Reticulum Ca ATPase (SERCA). It uses ATP hydrolysis to pump Ca into the SR where it is bound by Ca binding proteins Calreticulin and Calsequestrin. Ca is retained in the cell.

Question 14

What are the two mechanisms of Ca removal from the sarcoplasm that extrude Ca into the extracellular fluid?

Answer 14

The plasma membrane Ca ATPase (PMCA). It pumps 1 Ca out per ATP used. The second is the Sodium Caclium exchanged (NCX). It lets 3 Na ions into the cell to remove 1 Ca from the cell.

Question 15

An increase in muscle tension from successive action potentials is called?

Answer 15

Summation

Question 16

Maintained contraction in response to repetitive stimulation is called?

Answer 16

Tetanus

Question 17

What is the difference between fused and unfused tetanus?

Answer 17

In unfused tetanus the tension oscillates

Question 18

What is Treppe? Is it the same as summation?

Answer 18

Repeated stimulation of the muscle at low frequency can produce Treppe where each twitch relaxes to zero tension before the next twitch initiates. In Treppe successive twitches show greater peak tension.

Question 19

How does Treppe occur?

Answer 19

It could be due to residual Ca after each AP and an increase in Ca concentration. It could also be due to the fact that the muscle warms up and enzymatic reactions occur at a faster rate.

Question 20

What is a motor unit?

Answer 20

A somatic motor neuron and all the muscle fibers it innervates. (a single muscle fiber is innervated by only one motor neuron)

Question 21

Large motor units are typically found in what muscle type? With which muscle type are small motor units associated?

Answer 21

Large - Fast twich muscle (Type II).

Small - Slow twitch (Type I)

Question 22

What is motor recruitment and the Size Principle?

Answer 22

Smaller motor units are recruited first and as more force is required then larger motor units are recruited. The ability to recruit only a few muscle fibers gives the possibility of fine control.

Question 23

Order the different energy sources of ATP in muscle by it’s duration of supply to the musle

Answer 23

ATP (1-2 sec), Phosphocreatine (5-8 sec), Anaerobic metabolism of glucose (60 sec), Oxidative metabolism of glucose (2-4 hours), Oxidative metabolism of fats, carbs, and proteins (many hours).

Question 24

What are two causes of muscle pain? Discuss the role of lactic acid in both.

Answer 24

The burn of working muscle is produced by lactic acid buildup when anaerobic glycolysis is used. In the case of the DOMS it is not correlated with lactic acid levels and occurs day(s) after muscle use. It is likely due to damage or possibly an inflammatory response.

Question 25

Define muscle fatigue and explain the implications of it.

Answer 25

It is a decline in muscle tension as a result of previous contractile activity. Results in less maximal tension, decreased shortening velocity (Vmax) and slower rate of relaxation.

Question 26

What causes muscle fatigue? Is it due to ATP depletion?

Answer 26

It is caused by the depletion of Ca in SR, as well as, the buildup of lactic acid and Pi in the cells. It is NOT due to low ATP since a fatigued muscle still has quite high concentrations of ATP. (low ATP could result in rigor)

Question 27

What is High frequency fatigue?

Answer 27

It accompanies high intensity, short duration exercise. It is due to failure in the conduction of AP in the T tubule. Recovery is rapid.

Question 28

What is Low frequency fatigue?

Answer 28

It is seen with low intensity, long duration exercise. It is due to the buildup of lactic acid and Pi’s. TnC shows lower affinity for Ca at low pH. Myosin release ADP slower in low pH. Recovery is slow.