17. The regulation of muscle work and muscle-nerve connection: the motor unit

Question 1

What should be mentioned?

17. The regulation of muscle work and muscle-nerve connection: the motor unit.

Answer 1

Motor units

From neural activation to muscle contraction

Neuromuscular junction

Acetylcholine

Clathrin

Nicotinic acetylcholine

End plate potential (EPP)

Magnesium

Transmission

Drugs affecting

Fusimotor system

Fine-tuning od muscle tension

Co-Activation

Question 2

Motor unit - basics

Answer 2

A motor unit is made up of a motor neuron and the skeletal muscle fibers innervated by that motor neuron’s axonal terminals.

-Receptor gets a message, it sends it through the sensory side, with a afferent nerve, It gets to the CNS and on the acting side it will be sendt with a efferent nerve to the effector.

Question 3

From neural activation to muscle contraction (summary)

(picture, learn this!!)

Answer 3

Question 4

The Neuromuscular Junction

Answer 4

The Neuromuscular Junction:
Contraction of skeletal muscle fibers is elicited by nerve impulses in the motor nerve fibers to the muscle. The synapse between the neurons and the muscle fibers are called the neuromuscular junction.

One presynaptic AP elicits one AP in the postsynaptic cell.

Important with this connection is the acetylcholine (ACh). It is a neurotransmitter which will be realeased. This chemical signal binds to the nicotinic receptors of the muscle membrane and results in the opening of ligand activated cationic channels.

The opening of these cationic channels produces a local current (end plate potential, EPP) which is conducted to the fast, voltage gated sodium channels. The channels will open, which results in CA2+ influx into the terminal from extracellular fluid.

(eget flashcard med bilde)

Question 5

The Neuromuscular Junction

(picture)

Answer 5

Question 6

Acetylcholine

Answer 6

Acetylcholine is a neurotransmitter.
It is the chemical that motor neurons release in order to activate muscles.

Question 7

Clathrin – vesicle synthesis

Answer 7

-The mechanism of endocytosis is stimulated by CLATHRIN (which
is a contractive protein, attached to the inner membrane).

-To bring something from the outside of the cell inside, clathrin molecules combine at the cell membrane to form a clathrin- coated pit on the inside surface of the outer cell membrane. The pit then rounds and pinches off, trapping a section of membrane in a clathrin-coated vesicle. The membrane section, and the associated receptor proteins, are then carried into the cell for processing, disassembly, or recycling.

Question 8

Nicotinic acetylcholine receptor

Answer 8

• At the neuromuscular junction they are the primary receptor in muscle that controls muscle contraction.
• Composed of two alpha, two beta and one delta subunits.

Question 9

Nicotinic acetylcholine receptor (picture)

Answer 9

Question 10

Nicotinic acetylcholine receptor (picture, 3 states)

Answer 10

Question 11

End Plate Potential (EPP)

(picture + text)

LEARN!

Answer 11

• The neuromuscular junction is located in the middle of a muscle cell. Between the presynaptic and postsynaptic membrane there will be a synaptic cleft. The area of the postsynaptic membrane which points towards the cleft is called end plate.
• End plate potentials (EPPs) are the depolarizations of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane.
• Ligand binding to the acetylcholine receptor opens cation channels and end-plate potential (EPP) is generated. It is conducted with decrement (gradual decrease) to the neighboring voltage gated sodium channel and action potential (AP) is generated.
• Decremental conduction: the signal strenght decreases with the distance traveled.

Question 12

Role of Magnesium

Answer 12

Increases in EC magnesium concentration: provokes acetylcholine receptor and blocks functioning of the sarcomere.

It is extremely important in the case of the cattle, where extremely high calcium secretion into the milk after calving decreases plasma calcium level.

muscles will relax: parturient paresis happens.

Question 13

The physiological signal transmission in the motor unit

(picture, learn)

Answer 13

Question 14

Drugs Affecting Neuromuscular Transmission

Answer 14

Drugs of action similar to ACh: Nicotine. Same effect as ACh, but it can not be degraded by cholinesterase. Therefore concentraton is increased which results in a permanent depolarizaton - contraction lasts through minutes, hours - intensive spasm.

Cholinesterase Inactivators: ACh is not hydrolyzed, therefore extreme ACh cumulation occurs (nerve gas) - repetitively stimulate muscle fibers - spasm (for hours), Laryngeal spasm (lethal)

Curariform drugs: AChR is competitively blocked (ACh driven Na-channels can not open sufficiently) therefore depolarization can’t happen - no contraction, Paresis.

Blocking the ACh release: (Botulin Toxin) Paresis

Myasthenia Gravis: autoimmune disease - AChR blocking auto-antibodies - ACh can not be bound to the receptor resulting in the lack of signal transmission - Paresis

Treatment: Neostigmine (Cholinesterase inactivator). Result: ACh is accumulated, which stimulates the few intact AChR – so the muscle temporarily functions almost normally!

Fatigue of Myoneural Junction: In vivo it rarely happens (extreme exhaust). Experimentally: lack of ACh synthesis – no signal transmission (If we stimulate the nerve or the muscle separately, AP will be created in both places without a transmission of signals (due to the lack of AcCh))

Question 15

Motor unit (Picture)

Answer 15

Question 16

Morphology of muscle nerve connection

Answer 16

Muscle fibres are rich in fine branching structures at the end of a nerve fibre.
Nerve fibre and muscle fibre ratio may considerably vary according to the task of the given muscle. Muscles executing fine movements (e.g., ocular muscles) have a nerve fibre and muscle fibre ratio of 1:1, whereas, in other skeletal muscles it can even reach a 1:100 ratio.

Question 17

The Fusimotor System

Answer 17

Modified muscle fibres in skeletal muscles play a role in stretch- detection (receptor function) and in fine tuning of muscle tension. These specialized fibres (called intrafusal fibres) are located among the working fibres (extrafusal fibres, which give the majority of fibers).

We can find receptors also in tendons called Golgi tendon receptor organs.

Question 18

Fusimotor System - afferentation (picture 1)

Answer 18

Question 19

Fusimotor System - afferentation (picture 2)

Answer 19

Question 20

Fine-Tuning of Muscle Tension

Answer 20

Muscle spindle is sensitive to stretching. In case of the Myotatic Reflex (it’s muscle contraction in response to stretching ) efferentation returns to the same muscle where the afferentation (stretch of the muscle spindle ) is coming from.

The reflex is monosynaptic due to the Ia. afferentation directly activating (creating only one synapse) to a large motoneuron (α) (or a small motoneuron) in the spine chord.

Responses:

1, The motoneuron stimulate the Aα-efferent, which runs to the extrafusal muscle. Result is contraction, antigravitation (maintenance of posture). So the increasing stretching causes increased tension (contraction) in a monosynaptic way, without the influence of the cerebral motor center. This is the so called „servo-mechanism”.

2, Activation of fusimotor system (γ-loop) – Ia-afferentation – also runs to γ motoneuron – then γ-efferent runs to the contractile part of the muscle spindle – The result is stimulation of muscle spindle, resulting in the fine adjustment of muscle tension (maintaining tonicity), and in that way the system participates in the co-activation mechanism.

Question 21

Fine-Tuning of Muscle Tension (picture)

Answer 21

Question 22

Co-Activation

Answer 22

In addition to the „servo-mechanism”, the central nervous system (CNS) also participates in the activation of the fusimotor system.

Motor command of the cerebral center simultaneously stimulates both α- and γ-motoneurons, which is called co-activation. When the contraction is appropriately executed, both intrafusal and extrafusal fibres contract with the same rate and strength.

In case of suddenly increased load, however, the tension in extrafusal fiber is stronger than in the intrafusal.