Physiology of
locomotor module
NEUROMUSCULAR TRANSMISSION
Definition of neuromuscular junction: It is the area of contact between a nerve fiber and muscle fiber, It is also called the motor end plate.
Structure of neuromuscular junction:
1.As the nerve approaches the muscle it loses its myelin sheath and its axon is branched (axon terminals).
The tips of each branch is swollen like a bulb and called sole foot.
2.the sole foot is covered by neurolemma (contains voltage gated Ca2+ channels),
which will be continued with the sarcolemma (the outer membrane of the muscle fiber).
3.The sole foot contains vesicles that contain the neurotransmitter acetylcholine and mitochondria.
4.Each sole foot lies in a depression in the plasma membrane (Inner membrane of the muscle fiber),
called synaptic gutter.
5.The muscle membrane, at synaptic gutter, is thrown into many folds, called palisades (or junctional folds),
which greatly increases the surface area of end plate.
6.The sarcoplasm (the protoplasm of muscle fiber), at synaptic gutter,
contains mitochondria and rich of cholinesterase enzyme, which hydrolyzes acetylcholine.
7.The sarcolemma, at synaptic gutter, contains acetylcholine receptors.
8.There is no protoplasmic continuity between the nerve and muscle at myoneural junction. They are separated by the synaptic cleft.
-The synaptic cleft is the space between sole foot & synaptic gutter where acetylcholine is released from the sole foot.
Miniature end plate potential:
-It is a state of persistent localized subthreshold depolarization(0.5 mV in amplitude) of the muscle fibers at the motor end plate during rest.
-It does not reach the firing level so it does not lead to propagated action potential.
-It is caused by spontaneous random release of small amounts of acetylcholine due to continuous rupture of a few acetylcholinevesicles at the nerve terminals during rest.
Mechanism of Neuromuscular transmission:
-It is the process of relay of the action potential from the nerve to muscle fiber,It is carried out chemically by acetylcholine as follows:
1.When a motor nerve is stimulated it leads to propagated action
potential towards myoneural junction leading to depolarization
of the sole foot.
3.Ca++ cause rupture of acetylcholine vesicles, through
(Ca++ dependent exocytosis) leading to release of acetylcholine
into synaptic cleft.
2.Depolarization of the sole foot leads to opening of
voltage gated Ca++ channels and Ca++ influx into nerve
terminal
4.Acetylcholine binds to nicotinic receptors in the muscle
membrane leading to opening of "Ligand" gated Na+ channels
that leads to Na+ influx resulting in local depolarization at the
motor end plate known as end plate potential.
6.Once Acetylcholine produces its action
it is rapidly hydrolyzed by cholinesterase enzyme, which
prevents re-excitation of the muscle.
5.Under normal conditions, the end plate potential
reaches the firing level (- 40mv) which initiates an action
potential, that will be propagated along the surface of the
muscle
Properties of neuromuscular transmission:
1- One-way
(unidirectional)
2- Delay in
conduction:
3- Fatigue at
neuromuscular
junction:
Transmission of impulses at neuromuscular junction is delayed 4- Effect of
about 0.5-0.7 millisecond due to the time needed for:
ions:
At neuromuscular junction, the impulse conducted only from
the nerve to the muscle and not in the opposite direction.
a. Release of acetylcholine from the nerve terminals.
b. Diffusion of acetylcholine across the synaptic cleft.
c. Binding of acetylcholine with nicotinic receptors in muscle.
d. Increase of permeability of the muscle membrane to Na+
e. Increase in Na +influx till the firing level is reached.
-It is caused by rapid repeated stimulation
( more than 100 times/sec) of the motor nerve
-mostly due to depletion of acetylcholine vesicles
-Increase Ca++ ions in extracellular fluid causes rupture of
acetylcholine vesicles
-that increases acetylcholine release leading to increased
neuromuscular transmission.
-Increase Mg++ ions in extracellular fluid leading to stabilization of
acetylcholine vesicles decreasing acetylcholine release and
neuromuscular transmission.
PHYSIOLOGY OF SKELETAL MUSCLES
Functions of skeletal muscles:
1- Maintenance of erect posture & various body attitudes.
2- Help venous return & heat production.
3- Performance of voluntary acts.
The motor neuron pool
This is a collection of anterior horn cells that supply a skeletal muscle.
They are usually grouped together in 1 or 2 neighboring segments.
The motor unit (The nerve-muscle functional unit):
-The motor unit consists of one anterior horn cell + its axon + muscle fibers supplied by this axon.
-Each motor unit obeys all or non-law as all the muscle fibers in a single motor unit have the same level of excitability.
- In muscles which perform fine movements each motor unit contains 3-6 muscle fibers e.g. muscles of hand & eye.
-in muscles which perform gross movement each motor unit contains 100-200 muscle fibers e.g. muscles of leg & back.
NB:
-Skeletal muscles constitute 45-50 % of total body weight.
-They are under voluntary control.
-Their activity depends on their nerve supply.
MECHANISM OF MUSCLE CONTRACTION
I. Excitation-contraction coupling:
Definition: This is the process by which depolarization of the muscle fiber initiate contraction, when a nerve impulse
arrives at the motor end plate. involves the following steps:
1) Discharge of the motor neuron & arrival of the nerve impulse to the nerve terminal at the neuromuscular junction.
2) Depolarization of the nerve terminal at neuromuscular junction leading to
acetylcholine release, through Ca2+dependent exocytosis.
3) The acetylcholine crosses the synaptic cleft binds to the nicotinic receptors, at the motor end plate
leading to Na+influx, through ligand-gated Na+ channels results end plate potential.
4) When the end plate potential reaches the firing level, an action potential is generated and propagates on
either side of the muscle surface (the motor end plate usually lies in the middle of the muscle fiber)
as well as to the inside of the muscle fiber along the T-tubules.
5) Release of Ca++ from the sarcotubular system: When the action potential reaches the sarcoplasmic reticulum &
terminal cisterns via the T-tubules, it leads to opening of voltage-gated Ca++
-channel on the surface of the sarcoplasmic reticulum with subsequent Ca++ release into the sarcoplasm
-Ca++ diffuses to adjacent myofibrils where it binds strongly with troponin C.
II. The role of Ca++:
During relaxation:
-Troponin I is tightly bound to actin and tropomyosin covers
the active sites (ADP) on actin
-thus preventing the interaction of myosin heads with actin that cause contraction.
-So the troponin-tropomyosin complex constitutes the relaxing protein.
When Ca++ binds to troponin C:
-The troponin complex undergoes conformational changes that weakens the binding
of troponin I to actin and moves the tropomyosin laterally away from active site of
actin.
-This “uncovers” the active sites of the actin thus allowing these to attract the
myosin cross-bridge heads cause contraction to precede.
III. Molecular mechanism of contraction (Sliding, Walk along theory):
The muscle contraction occurs as a result of sliding of actin filaments in between thick myosin filaments through repeated formation and breakdown of cross linkages between
active actin sites and activated head of myosin cross bridges as follow:
1-Once Ca2+ level is increased in the sarcoplasm above critical
level, the ATPase activity of the myosin head become activated,
where it binds with and cleaves ATP.
But the ADP remains attached to the head.
2-At the same time, the troponin-tropomyosin complex binds
with Ca2+ exposing active sites on the actin filament that
attract the myosin heads and bind with them forming the cross
linkages.
3-Binding the head of the cross-bridge to the active actin site
causes a conformational change in the head leading to tilting of
the head, at the hinges, towards the arm of the cross bridge,
dragging the actin filament along with it, towards the center of
myosin filaments; this is called the power stroke.
-The energy required for the power stroke is already stored in
the head, from previously cleaved ATP.
5-The binding of the ATP
molecule causes detachment
of the myosin head from the active
actin site, at the same time;
4-Tilting the head of the cross-bridges allows release of the ADP
that were attached to the head and a new molecule of ATP binds
and cleaved.
6-ATP is hydrolyzed by ATPase activity of the myosin head. The released energy moves the myosin head back to its original position and partially
stored in the head for producing the next power stroke.
7-Thus, the heads of the cross bridges bend back and forth and step by step walk along the actin filament, pulling the ends of
two successive actin filaments toward the center of the myosin filament, so it is called Walk along theory
8-This process of binding, tilting and detachment of the myosin heads is repeated as long as ATP is available and Ca++remains above critical level.
Muscle relaxation
-As acetylcholine perform its action, cholinesterase enzyme breaks down acetylcholine within the synaptic cleft.
-The muscle action potential ceases. And Ca+2 release channels close.
-Ca2+ is pumped back into the sarcoplasmic reticulum by an active Ca2+ pump leading to decrease Ca++ concentration in the sarcoplasm.
-Ca++ is released from troponin C, while troponin I binds strongly with actin & tropomyosin covers the active sites of actin.
-The interaction between actin & myosin ceases and the actin filaments slide back to its resting position resulting in muscle relaxation.
NB: Both contraction & relaxation are active & need ATP. The ATP is required for:
1. The power stroke during the cross linkage.
2. Active Ca++ reuptake back into the SR, during relaxation.
3. Na+- K+ pumping through the muscle fiber membrane to maintain normal RMP.