Physiology Notes 2015 – 1 6 Dr. Ahmad .S.

Alarabi

Nerve & Muscle

Nerve
The neuron is the structural unit of the nervous system. The nervous system of the
human body contains about 1012 (trillion) neurons which are found in many shapes
and sizes. The neuron is composed of:

1- Cell body (soma): it contains the nucleus

and the other cell organelles (except the
centriole), so the neurons can’t divide.

2- Cell processes: they include:

A- Dendrites: they are multiple short
processes on the outer surface of soma.
These dendrites have receptors on its surface
that receives the signals (stimuli) and convey
it as electrical impulse toward the soma.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

B- The axon (nerve fiber): it is a single long process that conducts the impulses
away from the soma. The 1st part of axon (1st mm) is called the Initial segment
(Axon Hillock), which is the most excitable part of axon, because it has high density of
voltage gated Na+ channels. At the end of axon there are a number of terminal
branches, each branch end in many Synaptic knobs. These knobs possess vesicles that
contain a Neurotransmitter needed for signal transmission.

● The length of axon ranges from few mm to more than a meter, and the diameter
ranges from 0.1 to 20 microns. It contains Mitochondria, Neurofilaments,
Microtubules and Smooth Endoplasmic Reticulum.

● The axon is covered by 2 sheaths:

i- Neurilemmal sheath (outer sheath):

It's a single layer of Schwann cells covering
the whole axon in all neurons. It's important
for nerve regeneration after injury.
ii- Myelin sheath (inner sheath): it is
lipoprotein in nature made up of many layers
of Schwann cells. It covers some axons [except
at its origin, end and at Nodes ofRanvier (every
1 mm)]. It acts as insulator preventing the flow
of ions (electrical current). According to its
presence or absence, the nerve fibers are
classified into Myelinated & Unmyelinated .

● The Neurons are classified by 3 ways:

1- According to the structure into:

• Unipolar: present in spinal afferent neurons.
• Bipolar: present in some sensory pathways
[e.g. Visual pathway]. Multipolar Bipolar Unipolar
• Multipolar: present in the CNS [ventral Horn
of spinal cord [e.g. Alpha motor neurons].

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2- According to the function into:

• Sensory (afferent): conduct impulses (sensation) from receptors into CNS.

• Motor (effeerent): conduct impulses (action) from CNS into effector organ.
• Interneuron: form about 99% of all neurons. it's located inside CNS.
For more information, See the Autonomic NS chapter.

3- According to diameter and velocity into 3 groups (see the table page 14).

● The nerve fibers (axon) of neurons are classified also by two ways:

1- According to neurotransmitter released at its end (Adrenergic / Cholinergic).

2- According to its nerve fiber into (Myelinated / Unmyelinated).

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Resting membrane potential

(RMP) or (Polarization)

● Definition: it is the electric potential difference between the inner1 and outer2 surface
of the cell membrane during rest.

• It is present in all cells of the body with inner surface is ALWAYS negative relative to
the outer surface of the cell.
• It varies from cell to cell [ranges (– 9 in RBCs) to (– 100 in Skeletal muscles) m. volt.
• In medium sized nerves it is about (– 70 m.v).

● Causes of RMP

▪ To understand the causes of RMP, we have to know the following facts which are
applied for all membranes:

1- All the ions [+ve (Cations) or –ve (Anions)] pass through the leak channels in the
membrane with various degrees of (selective) permeability [the membrane is poorly
permeable to chloride and impermeable to proteins (Anions)].
2- The leak channels are permeable to K+ 50 times > Na+.
3- The concentration difference of K+ between ICF and ECF is about 30 times (> in ICF)
and of Na+ is 10 times (> in ECF) [please see the table (page 8) in introduction sheet].
4- The Voltage – Gated Na+ channels are fast while those of K+ are slow.

▪ By knowing these facts, we can understand that:

1- The high difference in concentration of K+ (30 times inside more than outside) and its
high permeability through the leak channels more than any other ion makes it
the most determinant ion in the creation of RMP.
So, when the K+ efflux (outflow) outside the cell in attempt to achieve the equilibrium
in its concentration, it changes the charge inside the membrane to the negative.

2- The amount of Na+ ions that influx inside the cell is not enough to overcome that of
effluxed amount of K+, while the Na+ is less permeable than K+ through leak channels.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

3- The chloride has minor role in the creation of RMP.

4- The proteins have no role in the creation of RMP.

[We conclude that the RMP is mainly due to K+ efflux (outflow)].

There is another cause that maintains the RMP which is known as Na+ – K+ pump.

Na+ / K+ pump

● Definition: it is an active pump presents in the membrane of all body cells.

It pumps 3Na+ outside the cell coupled with pumping 2K+ inside the cell.
The energy required for the action of this pump is utilized from ATP by the help of
ATP ase enzyme exist on the inside portion of this pump.

● Functions:

1- Contributes in creating part (only – 4 m.v) of RMP.

Outside

2- Maintain the Na+ & K+ concentration difference

across the cell membrane. Some Na+ enters the
cell during rest and more amounts enter during
action, and this pump returns the concentrations
back to normal.

3- If these excess amounts of Na+ weren't removed,

they well pull amounts of water (by osmosis) and
the cell will swell until burst. So this pump Inside
controls the cell volume.

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Action Potential

● Definition: it is the changes in the electrical potential difference between the inner and
outer surface of the membrane that occurs during action (applying a stimulus).

There are some terms that we have to know regarding the action potential process:

1- Stimulus: it is an environmental change (Stimulus) that causes the opening of gated

Na+ channels → Na+ influx → change of the inside charge from the negative resting
charge (in RMP) to positive charge.

2- Depolarization: it is the change of membrane potential that ↑ from RMP (– 70 m.v)

until reaches a positive potential (+35 m.v) due to the application of suitable stimulus
that will causes Na+ influx (the magnitude of change = 105 m.v).

3- Repolarization: it is the return of membrane potential from (+35) again to its resting
level due to stopping Na+ influx and ↑ K+ permeability (by K+ efflux).

4- Firing level: it is the reaching of membrane potential to a level of (+55 m.v) at which
all gated Na+ channels open → Action Potential.

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The process of action potential depends on the presence of 2 voltage gated ion channels
[Voltage – gated Na+ channels / Voltage – gated K+ channels] in contrast to the leak
channels that are involved in the creation of
RMP.

a- Voltage – gated sodium channels:

These channels have 2 gates:

i- Activation gate (at the outer surface):

during RMP (– 70) these channels are
closed. These channels open in
response to depolarization. Some of
them opens at (– 63) but almost all of these channels open at the firing level (–55).

ii- Inactivation gate (at inner surface): the closure of these channels occurs slowly
when the membrane potential increases > (– 55 m.v) and almost all of these gates
will close at the end of depolarization at (+35 m.v). These gates will not reopen
again until the membrane repolarizes, so the Na+ channels will not activate again
(after their stimulation) until the membrane repolarizes.

b- Voltage – gated potassium channels:

These channels have only one gate at the inner
surface. These channels are closed during rest.
They start to open (activate) late in
depolarization and becomes completely
opened by the end of depolarization and
continue to be opened during Repolarization.

Description of action potential

If we recorded the electrical changes of AP by 2 microelectrodes one inside1 and the

outside of the cell, the produced diagram will be in the form of spike & after potential.
The events of this recording will be in the following steps:

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

1- Stimulus artifact: it is the time of application of the stimulus.

2- Latent period: it is the time passed between the application of the stimulus and the
recording of action potential. This period depends on the velocity of conduction of the
nerve & the distance between the stimulus and the electrodes.
3- The spike: it is a rapid process (2 m.seconds) with high magnitude changes (105 m.v).
It is composed of:

a- Ascending limb: it represents the depolarization [i.e. change of MP from (–70) to

(+35)]. It is due to ↑ Na+ permeability 1000 – 5000 times when the activation gates of
the V – G Na+ channels opens (in response to stimulus) → Na+ influx → ↑ MP toward
(+35).The 1st part of ascending limb (1st 15 m.v) [(–70) to (–55 or firing level)] is slow.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

b- Descending limb: It represents the 1st 70% of Repolarization [i.e. returning of the MP
from (+35) back to near RMP]. It is due to stoppage of Na+ inflow [due to closure of
inactivation gates] and starting of K+ outflow [due to activation (opening of the gates)
of Voltage – Gated K+ channels].

4- After depolarization (Negative after potential): it represents the last 30% of

Repolarization. It is a slow process because at this time the gates of some of the
Voltage – Gated K+ channels close. Its duration is 4 m.seconds.

5- After hyperpolarization (Positive after potential): it is the reaching of membrane

potential to a level beyond the RMP [(more negative to about (-90)] and gradually
returning back to the RMP. This is because that many voltage – gated K+ channels
remain opened after Repolarization → excess K+ diffuse out.
It's also due to hyperactivity of Na+ – K+ pump.

Propagation of action potential

One of the properties of AP that it can spreads in both directions away from the
stimulated segment. The method of conduction
depends on the type of nerve fiber.

1- Conduction in Unmyelinated nerve fibers:

It is by local circuit mechanism.

• The resting segment has +ve charge outside

and –ve charge inside, while the activated
segment has –ve charge outside and +ve
charge inside.
• The local circuits occur between a depolarized
segment and adjacent resting segment.
• The newly depolarized segment depolarizes its
adjacent segment in the same way and so on
till the depolarization wave reach the end of
nerve fiber.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

• The propagation of action potential (depolarization wav) along the nerve fiber is called
nerve impulse.

2- Conduction in Myelinated nerve fibers: It is by Saltatory conduction.

• It is a similar to the conduction in unmyelinated nerve fibers, but the local circuits
here occurs between the adjacent nodes of ranvier (not the adjacent segments) because
the myelin sheath acts as an insulator of electricity (passage of ions). So the
depolarization wave jumps from node of ranvier to another (Saltatory conduction).
• It is 50 times more rapid than conduction in Unmyelinated Nerve Fibers.
• It needs less energy than conduction in Unmyelinated Nerve Fibers.

» Orthodromic & Antidromic conduction:

When a stimulus generates action potential in
the middle of an axon, it will propagate and
travel in 2 impulses in opposite directions,
These impulses are:

● Orthodromic Conduction:
The impulses pass toward axon terminal.

● Antidromic Conduction:
The impulses pass toward the soma.
These signals die out at first synapse
[since synapse, unlike axon, permits conduction in one direction].

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Excitability
● Definition: It is the ability of living tissue to respond to an adequate stimulus.
The most excitable tissues in the body are the Nerve and Muscle.

Excitability changes during AP

1- During local response up to the firing level, the excitability is increased.
2- Absolute refractory period: It is the period during which the nerve fiber can’t
respond to any stimulus whatever it was strong (Excitability is lost, i.e. = Zero).
It coincides with ascending limb and 1st 1/3 of descending limb of the spike.
This is because the Voltage – Gated Na+ channels are either:

• Fully activated [the activation gates are open (in ascending limb)].
• Inactivated [the inactivation gates are closed and will never open until the
membrane repolarized (in 1st 1/3 of descending limb)].

3- Relative refractory period: It is the period during which the membrane to be

excited, it needs the strength of the stimulus to be more than normal, i.e.
(stronger stimulus). It coincides with the remaining 2/3 of descending limb of the
spike, and it lasts from ¼ to ½ the absolute refractory period.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

4- Supernormal phase of excitability:It is the phase during which excitability

raises above normal. it coincides with after depolarization.

5- Subnormal phase of excitability:It is the phase during which excitability is

slightly reduced, and then becomes normal. It coincides with after hyperpolarization.

Factors affecting excitability of nerve

1- Factors that decreases excitability (membrane stabilizers):

• High Ca++ in ECF [↓Na+ permeability]. • Local anesthetics [↓ Na+ permeability].

• Low K+ in ECF. • Low Na+ in ECF.
• Acidosis (→ ↑ plasma Ca++ ). • Hypoxia (lack of O2).
• Cooling (Hypothermia). • Pressure.

2- Factors that increases excitability:

• Low Ca++ in ECF. • High Na+ & K+ in ECF.

• Alkalosis ((→ ↓ plasma Ca++). • Warming (Hyperthermia / Fever).

Stimulus

● Definition: It is an environmental change that causes starting diffusion of Na+ to

the inside of cell.
● Types: [Electrical / Chemical (Hormone or NT) / Mechanical (e.g. pressure) / Thermal
(e.g. cooling or warming) / Electromagnetic (e.g. light rays)].

● Effects of stimulus: It depends on:

I- Intensity (strength) of the stimulus:
The stimuli are classified according to their strength into:

( Threshold / Suprathreshold / Subthreshold )

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► Threshold stimulus: It is the minimal stimulus needed to excite the nerve & produce
AP (propagated response) [i.e. can raise the membrane potential (by Na+ inflow) till
reach the firing level (-55)].

► Suprathreshold stimulus: It has more intensity than threshold stimulus, but will
produce the same response as threshold (AP with the same magnitude and duration).

► Subthreshold stimulus: It has less intensity than threshold stimulus.

Instead of producing propagated AP, subthreshold stimulus causes one of two
localized (non propagated) changes in the membrane potential, which are:

1- Electrotonic potential: It is a mild change in the MP below 7 m.v change (below

– 63 m.v) that occurs as a result of application of low subthreshold stimulus.
These changes will not cause actual response (AP) [i.e. no opening of Na+ channels].

2- Local response: It is the change in

membrane potential between (7 – 14 m.v)
when applying a subthreshold stimulus
stronger than that cause electrotonic
potential. In this type of potential there is
an actual response, but it can’t propagate
(doesn’t produce AP). If the stimulus
strength ↑ to reach the change in MP to 15
m.v (-55 / firing level), this potential will
become an action potential (and
propagate).

All or none law

It states that either the nerve (tissue) responds maximally or does not respond at all when
applying a stimulus with suitable strength to cause AP (threshold / suprathreshold). The
tissues that obey all or none law are:

1- Single nerve fiber. 3- Both atria or both ventricles of the heart.

2- Single skeletal muscle fiber. 4- Visceral (single unit) type of smooth muscle.

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II- Rate of rise of intensity of the stimulus:

If a subthreshold stimulus is applied to
the nerve and its intensity is increased
slowly, the nerve will not respond (will
not produce AP even if the stimulus
becomes threshold) because of the
accommodation of the nerve.

But if the intensity of the subthreshold

increased rapidly, the accommodation
will not be observed and this increase in
intensity → generation of AP.

III- Duration of the stimulus:

For the stimulus to be effective, it should be applied (stay on the nerve) for a certain
time called excitation time.

The relation between intensity of

stimulus and its duration (excitation
time) is expressed by Strength Duration
Curve (Excitation Curve), where the
stronger the current (Strength), the
shorter the duration needed to excite up
to a certain level called minimal time.

► Minimal Time (T): the minimal time needed by the stimulus to excite, and below which
no excitation will occur whatever the strength of the stimulus was.

► Rheobase (R): the minimal strength that can excite below which no excitation will
occur whatever the duration of application was.

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► Chronaxie: it's the time needed by a stimulus (double the Rheobase) to excite.
It's a measure of excitability (The shorter the Chronaxie, the higher the excitability).

 Thick Myelinated nerve fiber (Chronaxie = 0.1 m.sec) High excitability.

 Thin Myelinated nerve fiber ..(Chronaxie = 0.3 m.sec) Moderate excitability.
 Unmyelinated nerve fiber …. (Chronaxie = 0.5 m.sec) Low excitability.

Mixed Nerves
The peripheral nerves are made up of many axons that vary in (Diameter / Velocity of
conduction / Threshold of stimulation). As a result of this variation, the action potential
in mixed nerve has the following features:

1- Does not obey all or none low (i.e. has a graded response), where:
a- Subthreshold Stimulus: will produce no response.
b- Threshold stimulus: some axons (with low threshold) fire → small AP is observed.
c- Suprathreshold stimulus: more axons fire → increased AP observed.
d- Maximal stimulus: leads to excitation of all axons → maximal electric response.
e- Supramaximal stimulus: the same effect as Maximal stimulus.

2- Recorded Action Potential has Multiple Peaks called

(Compound Action Potential).
This is because the nerve is composed of axons of varying
velocity of conduction.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Types of nerves

Most
Diameter in Velocity in Spike
Group Example micron (µ) (meter/sec) Duration
susceptible
to

A • Myelinated fibers of 10 –
Divided Almost all of the 2 – 20 0.5 m.sec Pressure
Somatic [aff & eff] 120
into
• Somatic motor 60 –
Alpha (α) 10 – 20
• Proprioception 120
• Fine touch
Beta (β) • Proprioception
5 – 10 30 – 60

• Somatic motor to
Gamma (γ) Muscle Spindle
3–5 15 – 30

• Temperature (cold)
Delta (δ) • Crude touch
2–3 10 – 5

• Myelinated Autonomic O2 lack

B Preganglionic
1–2 5 – 10 1 m.sec ( Hypoxia )

C • Unmyelinated fibers
• Slow pain
• Temp (hot) Local
Less than 1 0.5 – 2 2 m.sec
• Postg. Autonomic Anesthesia
[> ½ sensory fibers in
most peripheral N]

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Skeletal Muscle

Physiologic Anatomy

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

The skeletal muscles form about 40% of the body. Each muscle is composed of a number
of muscle fibers arranged parallel to each other. Each ms. fiber is cylindrical in shape
with about 10 – 100 micron (µ) in diameter.

• Each fiber is composed of has:

• Cell membrane (Sarcolemma).
• Cytoplasm (Sarcoplasm) that contains the nucleus and other cell organelles.
• Contractile elements (Myofibrils).
• Two types of tubules [Longitudinal Tubules / Transverse (T) Tubules].

Each myofibril apparently shows alternating

bands [light (I) band & dark (A) band].

• The I band is bisected by Z - line.

• The A band is bisected by H band.

• The sarcomere (the unit in the myofibril)

is the distance (segment) between two
successive Z lines. The presence of dark
(A) and light (I) bands gives the skeletal muscle its striated appearance.

• The myofibril is made up of two types of finer myofilaments [when fully relaxed]:

I- Thin filament (actin filament): each myofibril contains about 3000 thin
filaments. It extends from the Z line toward the center of sarcomere (middle of H band),
but not reaching it (when the ms. Fiber is fully relaxed). This filament is composed of:

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

1- Actin: it is formed of globular

molecules called (G actin molecules)
that are arranged in two chains twisted
with each other in spiral manner.
Each molecule has on its side an active
(binding) site for binding with myosin
head during cross bridging of actin and
myosin filaments (during contraction).

2- Regulatory proteins:
They regulate the interaction between
actin and myosin. These proteins
include:

• Tropomyosin: It is located in the groove between the 2 chains of actin.

It covers the myosin binding site (on actin molecule) so it will inhibit the
binding (action).

• Troponin: It is a small globular protein located on every revolution of actin helix

(every 0.04 µ). It is composed of 3 loosely bound protein subunits:

a- Troponin T: binds the other troponin components to tropomyosin.

b- Troponin I: covers the myosin binding site on actin molecule, i.e. inhibits
their interaction).
c- Troponin C: binds with Ca+ that initiates the contraction.

II- Thick filament (myosin filament):

-It is present in the middle of
sarcomere [forming the (A) band].
-There is a small projections
(cross-bridges) arise from this
filament except at its center (H band).
-Each myosin filament is made up of
myosin molecules.

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- Morphologically, each myosin molecule is composed of:

► 2 Myosin Heads (side by side): each head has 2 active sites:

• One for binding with actin.

• One has ATP ase activity
(splits ATP) to liberate the
energy needed for action.
► Arm and Tail.

- In each molecule, there are 2 flexible sites (hinges):

• Between the Arm and Head.
• Between the Arm and Tail.

- The infrastructure of each myosin molecule is made up of 6 polypeptide chains:

• 2 Heavy chains: form the [Tail – Arm – (2 heads)].
• 4 Light chains: control the function of head during the contraction process.

- In the thick filament, the myosin molecules are arranged as the following as:
• Side by side (each 6 molecules arranged around the circumference
separated by 60°) with 0.04 µ distance between each 6 molecules.
• End by end (with 1/2 the myosin molecules on the right and ½
on the left).

Note: The tails of the molecules form the body of the filament, and the arms and heads
form the cross bridges.

Tubular network of Sarcoplasm

The sarcoplasm has 2 types of tubules:

1- Longitudinal tubules:
These tubules form the sarcoplasmic reticulum which runs parallel to the myofibril.
At their ends (near T tubules) they enlarge to from chambers called Cisternae.

It stores the Ca++ in high concentration (10000 folds) in their Cisternae because they
have Ca++ pumps.

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2- Transverse tubules (T – tubules):

They are invaginations (infolds) of the sarcolemma that extends across the interior of
the muscle fiber (penetrate it).
They contain an ECF, and they run parallel to Z lines (each sarcomere has 2 T tubules
at its end near the Z lines).

The T – tubules transmit the action potential to the interior of the ms. fiber (especially
to the cisternae).

Neuromuscular junction
(Motor End Plate)

● Definition: It is the area of contact between motor nerve fiber and muscle fiber.
Near the ms. fiber, the nerve fiber looses its myelin sheath, and the neurilemma
becomes continuous with sarcolemma. Axon → several branches, each branch →
multiple synaptic knobs.

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The motor end plate (MEP) composes of:

1- Synaptic knob: it contains:

• In its cytoplasm: multiple synaptic vesicles containing the NT (which is ALWAYs
Ach in the MEP), and multiple Mitochondria [to provide energy for Ach formation].
• In its axolemma: multiple Voltage – Gated Ca++ channels.

2- Synaptic cleft: it contains the enzyme that destroys the Ach (Acetylcholine Esterase).

3- Synaptic gutter: an invagination in the sarcolemma that is involved in MEP.

It contains multiple Ach gated ion channels. At the bottom of this gutter, there are
numerous smaller folds of sarcolemma called secondary synaptic clefts
(Subneural clefts), it increases surface area on which Ach will act.

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Notes:
1- Motor Unit: it means a single motor
neuron and the ms. fibers it innervates.
The number of muscle fibers in the
motor neuron of muscles that perform
fine movement (e.g. laryngeal muscles)
is small (3 – 6) while that perform
gross movement is large (100 – 200).

2- Motor Pool: the number of neurons (AHC) that supply a single sk. Muscle.
The motor pool is composed of multiple motor units.

Mechanism of Neuromuscular Transmission

The crossing of nerve impulse to the supplied muscle occurs in the following steps:

1- When the nerve impulse (AP) reaches the synaptic knob → depolarization of its
membrane.
2- This depolarization (AP) will activates the voltage – gated Ca++ channels →
Ca++ influx.
3- The Ca++ inside the synaptic knob → release of Ach from its vesicles into synaptic
cleft (by exocytosis).
4- Ach binds to Ach – gated ion channels in the synaptic gutter → its activation (opening)
5- The opening of Ach – gated ion channels → influx of large amount of Na+ from ECF
into the sarcoplasm at area of MEP → localized partial depolarization at MEP called
End Plate Potential (EPP).
6- When the EPP reaches the firing level → AP that will propagate all over the
sarclemma. This potential called Muscle Action Potential.
7- Once released Ach binds to its channels and causes the AP, it will rapidly be hydrolyzed
by the enzyme Choline Esterase into Acetic acid & Choline. This rapid destruction
prevents re-excitation after recovery from 1st action potential.

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Properties of Neuromuscular Junction

1- Unidirectional conduction [from the nerve to the muscle, not the opposite].

2- Synaptic delay (about 0.5 m.sec).

3- Fatigue: it is ↓ response of NMJ as a result of rapid repetitive stimulation, which will

lead to depletion of Ach (because Ach release exceeds the Ach synthesis).

4- Effects of Ions:
 ↑ Ca++ in ECF stimulates the transmission by causing rupture of Ach vesicles.
 ↑ Mg++ in ECF inhibits the transmission by ↓ Ach release.

5- Effects of Drugs on NMJ Transmission:

Stimulants:
 Drugs which have Ach like action [e.g. Carbacol - Methacholine].
 Drugs which inactivate the cholinesterase [Anticholinesterases (e.g. Neostigmin)]
Inhibitors: Neuromuscular blockers (Muscle relaxants) [e.g. Curare].
They compete with Ach on the same receptors at MEP.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Myasthenia Gravis

● Definition: it is a hereditary1 autoimmune2 disease affecting 1 every 20,000 persons

(more in females). It's characterized by weakness of skeletal muscles due development of
antibodies in the body against its own Ach activated ion channels.

This disease is treated by Anticholinesterases [e.g. Neostigmin].

Comparison between the electrical events in the muscle and nerve

AP in Nerve AP in skeleta. Muscle

RMP -70 m.v -90 m.v

Firing level 15 m.v Depol. (-55 m.v) 40 m.v Depol. (-50 m.v)

Complete depolarization at +35 +40

Magnitude of AP 105 m.v 130 m.v

Duration of spike 0.5 – 2 m.sec 2 – 4 m.sec

After potential Shorter Longer

Velocity of conduction 0.5 – 120 meter/sec 5 meter/sec

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Mechanical response of the muscle

When a muscle is stimulated by single adequate stimulus, it will responds by contraction
(shortening) followed by relaxation, this response called Simple Muscle Twitch.
The recording of simple muscle twitch showing 3 periods:
• Latent period (10 m.sec).
• Contraction period (40 m.sec).
• Relaxation period (50 m.sec).

Mechanism of Contraction
(Excitation Contraction Coupling)

It is the process by which AP that reaches

the muscle fiber initiates contraction.
These events start after the arrival of AP to
the sarcoplasm at MEP area.
1- The arrived AP is transmitted through
the T – tubules to the interior of ms. fiber.
2- The AP crosses from the T tubules into
the cisternae. This will lead to opening of
voltage gated Ca++ channels in its wall →
release of Ca++ into surrounding sarcoplasm.

3- In the m. fiber, the released Ca++ binds to the Troponin C → lateral movement of
Troponin – Tropomyosin complex → uncovering the myosin active site on Actin.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

4- The uncovering of actin sites leads to

binding of the myosin head to these sites.

While the myosin head binds, it uses its

ATP ase activity to hydrolyze the ATP to
liberate the energy, which will be used
during the contraction process
[ATP → ADP + P (energy)].
5- The attachment of myosin head to its active site will leads to tilting of the myosin head
centrally and dragging the actin with it, this is called Power Stroke.
The energy used for power stroke is that was liberated on ATP hydrolysis.

6- After this tilting, a new ATP molecule binds to myosin head → detachment of the
myosin head from actin and its returning to the previous untilted position to start new
power strock.

7- The cycles of (Attachment1 / Tilting2 / Detachment3) will proceeds until the load on the
muscles exceeds its ability for more shortening.

Muscle Relaxation
When the stimulation by motor neurons (AP) stops, the Ca++ pumps on the cisternal
membrane start to reuptake Ca++ from the Sarcoplasm into Cisternae.
This will lowers the Ca++ concentration → detachment of Ca++ from Troponin C →
returning of Troponin – Tropomyosin complex to cover the actin binding sites → myosin
head unable to attach to actin → relaxation of muscle fiber to its previous resting length.

Types of muscle contraction

The contraction is of 2 types

1- Isotonic contraction: Shortening of the muscle during contraction with constant

degree of tension.

2- Isometric contraction: Contraction of the muscle fiber without ↓ length (shortening).

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Isotonic Isometric

Tension Constant Rises markedly

Length Decrease Constant

Contraction of extensors
Contraction of biceps
Example to left an object
of lower limb to support
the body against gravity
Work Done No work

Mechanical efficiency Relatively High Zero

More, as ms performs
Energy needed external work
Less

Long, due to
Duration Inertia & Momentum
Short

Note :
• The muscles in the body can contract by the 2 mechanisms.
• Most contractions are composed of the 2 types [e.g. when lifting an object, the muscle
first contracts isometrically then isotonically].

Factors affecting contractility

1- The type of the muscle fibers (Red or Pale):

• Every muscle in the body composed of 2 types of fibers known as:

• Fast (Pale)
• Slow (Red)

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Fast (pale) Slow (red)

Short rapid ms. contractions Slow prolonged ms. contractions
Function [e.g. jumping short distance [support of body weight against
eye movement,] gravity]

Fatigue Easily Not easily

Sarcoplasmic Extensive for rapid Ca++
Less extensive
reticulum release

Glycolytic Large amount (for rapid

Smaller amount
enzymes release of energy)

Mitochondria Few Increased number

Blood supply Less extensive More extensive

Myoglobin
Little amount Large amount
(stores O2)

2- Temperature: Warming leads to stronger and faster contraction, while the cooling
has opposite effect.
3- Fatigue:

Definition: the decrease in response (contraction) of the muscle as result of

rapid repetitive stimulation (prolonged strong contraction).

The contraction becomes (Weaker & Slower), while relaxation is (Slower & Incomplete).
It is because of:

• ↓ Energy sources [mainly Glycogen & ATP], due to reduction of blood flow.
• Accumulation of metabolites → depresses contraction & lead to pain sensation.
• Depletion of the Ach stores at nerve terminals.

4- Frequency of stimulation (Stair-Case Phenomena) / (Frequency-Tension relationship):

When a series of constant stimuli are applied to skeletal muscle at a high frequency
(Subtetantic frequency), there is a gradual increase in the strength of contraction in the
1st few twitches (1st 10 - 50 twitches), then the twitches reaches a Plateau.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

4- Initial length of the muscle:

This is represented by the (Length – Tension relationship [Starling’s law].

Starling’s law: it states that the strength of contraction (during isometric contraction) is
directly proportional to the initial length of the muscle (length before
contraction) within limit (the limit is the resting limit).
Notes:

• Resting length: the length of relaxed muscle inside the body (it's > equilibrium length).
• Equilibrium length: the length of relaxed muscle cut free from its bony attachments.
• Active tension: the tension developed during Isometric contraction.
• Passive tension: the tension developed during stretch of the muscle, due to presence
of elastic components. It's proportionate with initial length of muscle without limits.
5- Load on the muscle:
(Load – Velocity relationship):
When the muscle is allowed to shorten (isotonic contraction), the velocity of contraction
(shortening) is inversely related to the load on the muscle.
That is mean, the muscle that bear light weight (or no weight) contracts (shortens)
rapidly; while the muscle that contract against heavy weight contracts more slowly.

Rigor: it is a state of extreme rigidity (contraction) develops in the muscle as a

result of depletion of ATP, because the ATP is needed for separation of
cross bridges from actin.
When this condition occurs after death, it is called Rigor Mortis.

The rigor mortis has medicolegal importance because it helps in determination of time of
death. It starts after 2 hours from death (replacing the primary flaccidity), and reaches a
maximum level after 18 hours, and disappear after 24 hrs when the muscles proteins are
destroyed by bacteria (Putrefaction), and then a secondary flaccidity will appear.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Factors responsible for

gradation of ms. activity

The muscles can contract with various degrees of contraction by the following means:

a- Gradation of strength of contraction: It's due to 2 factors:

1- The number of discharging motor units (i.e. Number of motor units activated).
The more motor units discharging the more power of contraction.

2- The frequency of discharge in individual nerve fiber [the more frequency, the
stronger contraction]. But if the speed of stimulation was very rapid, it may
lead to Tetanus [because enough Ca++ is maintained in sarcoplasm between the
action potentials].

b- Gradation of the onset of contraction:

It's due to asynchronous activation of motor units (i.e. not activated at the same time).

• Electromyography:
It is the record of electrical activity of the muscle by either by:

• Metal disc electrodes placed on the skin over the muscle.

• Hypodermic needle electrodes inserted in the muscle to record the activity of
a single muscle fiber

• Effects of muscle denervation:

This is called lower motor neuron lesion (LMNL). It leads to:

Denervation hypersensitivity: muscle becomes extremely sensitive to circulating Ach.

Fibrillation: Fine, irregular, spontaneous contractions of individual fibers that can't
be seen
Atrophy: the muscle decrease in size, and muscle fibers are gradually replaced by fibrous
and fatty tissue.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Smooth Muscles

The smooth muscles are composed of few smaller fibers (2 – 5 μ) diameter, and
(50 – 200 μ) length. They are also called plain muscles because they have no striation.

Types: The smooth muscles are generally divided of 2 types [Multiunit / Single unit].

Single unit
Multiunit
(visceral)
Arrangement of Adherent to each other with
ms. fibers Discrete fibers
many gap junctions
Contraction of Each fiber independent The fibers contracts in
fibers on the others (doesn’t obey functional syncitium
all or none law) (obey all or none law)
Controlled by Mainly non nervous,
Mainly autonomic N.S
e.g. Hormones
Mech. Of Local depola. Caused by Spontaneous depolarization
contraction the NT (enough to elicit [act as pacemaker
contraction because the (self excitatory)]
fibers are very small)

Unable Able
Ability to contract
[because of its dependence [because some fibers
spontaneously on nerve supply]. are self excitatory].

- Ciliary muscles Wall of most viscera

Examples - Iris (e.g. Gut, Bile ducts, uterus
- Piloerector muscles and many blood vessels)

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Electrophysiology of
Smooth Muscle

The RMP of the sm. Muscle is about (– 50) to (– 60) m.v.

The Action Potential doesn’t occur normally in most multiunit sm. Muscles.
The action potential in visceral (Single unit) Smooth Muscles differ from that of
skeletal muscles in 3 aspects:

1- Its phases and its shape during the recording of electrical activity.
The AP of visceral smooth muscles may occur in 3 forms:

a- Spike potential [similar to sk. muscle]:

It is an action potential with short
period (10 – 50 m.sec) that occurs in
most single unit sm. Ms with short
periods of contraction.

b- AP with plateau [similar to cardiac muscle]:

It is action potential with longer period
[hundreds to thousands of m.seconds] that
occurs in types of muscles that shows
prolonged periods of contraction (e.g. uterus).

c- Slow wave potentials [pacemaker wave]:

This type of action potential occurs without extrinsic stimulus (in self excitatory
fibers), where the membrane potential is spontaneously & gradually reduced till it
reaches the firing level (– 35 m.v) leading to Action Potential.

2- The AP is mainly due to Ca++ inflow (not Na+) [because the sm. Ms. have more
voltage – gated Ca++ channels & few voltage – gated Na+ channels].

3- The AP is slow in all of its 3 forms in sm. Ms. compared with that of sk. Ms.

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Physiology Notes 2015 – 1 6 Dr. Ahmad .S. Alarabi

Excitation contraction coupling in sm. Ms

It is nearly similar to that of sk. Ms, but differs from it in 3 aspects:

1- Source of Ca++ that initiates the contraction is from ECF through V – G Ca++ channels.

2- Regulation of contraction by Ca++:

Instead of the Troponin, the smooth muscle has another regulatory protein called
calmodulin. It is activated by ↑ Ca++ → activation of myosin kinase → contraction.
The process of relaxation is mediated by ↓ Ca++ → inhibition of [calmodulin & MK],
and activation of [myosin phosphatase] → relaxation.

3- The frequency of cycling of the cross bridges is less than that of sk. Ms.

Comparison of mechanical activity between sk. & sm. Muscles

Skeletal ms Smooth ms

Less energy [1/10 to

Energy required More energy
1/300 of that of sk. Ms.]

Onset of cont. & relax. Rapid Slow

% of shortening during
1/3 its stretch length 2/3 its stretch length
contraction
More powerful Less powerful
Force of contraction [6 kg/cm2]. [4 kg/cm2].

With my Best Wishes

Dr. Ahmad Alarabi

2015 - 2016

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