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PHYSIOLOGY OF
NERVE AND MUSCLE CELLS,
NEUROMUSCULAR JUNCTION
AND
AUTONOMIC NRVOUS SYSTEM:
LECTURE 14
B Y: ASSISTANT PROFESSOR
DR. FARAH NABIL ABBAS
O B J E CT IV E S :
AT T H E E N D O F T H E L E C T U R E YO U S H O U L D B E A B L E TO
•Quick revision of anatomic characteristics of smooth
muscles.
•Explain the terms unitary and (multiunit) smooth
muscle and differentiate each type.
•Comparison between the electrical properties of the
smooth Muscle from the skeletal muscle.
•Understand the molecular basis of contraction of the
smooth muscle as compared to the cardiac and skeletal
muscle.
•Illustrate latch bridge and plasticity in th esmooth
muscle.
THE SMOOTH MUSCLE:
Characteristics
• Lack striation
• Lack sarcomeres
• Found in walls of hollow organs and supports
visceral function
• Have poorly developed sarcoplasmic reticulum
and lack T tubules.
• Lack troponin and instead they have calmodulin
• Slowly contracting muscles
THE SMOOTH MUSCLE:
Characteristics
• Can produce more force than some skeletal
muscle and more prolonged contractions with
less energy
• Contain less number of mitochondria.
• Actin and myosin grouped into bundles tie in
dense bodies
• Function somewhat independently of the NS
• All innervated by neurons of the autonomic NS
THE SMOOTH MUSCLE:
Actin and Myosin Organization
THE SMOOTH MUSCLE:
Characteristics
• Contains three filament types
a) Thin (Actin): tie to dense
bodies similar to Z lines
b) Thick (myosin): much larger
than in skeletal
c) Intermediate: non
contractile fibers
• These filaments are not
arranged in a regular pattern
as in striated muscle,
• as a result smooth muscle can
operate over a broader range
of stretch.
Smooth Muscle Filaments
Anatomic Consideration:
• Smooth muscle is distinguished anatomically from other muscles
because it lacks visible cross-striations.
• That is although actin and myosin are present and slide on each
other, they are not arranged in regular arrays as in skeletal or
cardiac muscle. Smooth muscle also contains tropomyosin, but not
troponin.
• Large numbers of actin filaments are attached to the so-called
“dense bodies”, with myosin filaments scattered among the actin
filaments.
Anatomic Consideration:
• There is a sarcoplasmic reticulum, but it is poorly
developed.
• In general, smooth muscles contain few mitochondria
and depend to a large extent on anaerobic glycolysis for
their metabolic needs.
• In general, smooth muscle can be divided into unitary
(visceral or single-unit) and multiunit smooth muscle.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle :
•The term “unitary” is confusing because it
does not mean single fibers; but a mass of
hundreds to thousands of smooth muscle fibers
that contract together as a single unit (syncytium).
•Unitary smooth muscle occurs in large
sheets and is found primarily in the walls
of hollow viscera; including the musculature of
the intestine, bile ducts, ureters, uterus and many
blood vessels.
•The cell membranes of these muscle
fibers are adherent to one another at
multiple points so that force generated at
one muscle fiber can be transmitted to
the next.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle :
•It has low-resistance bridges where the
membranes of two adjacent cells fuse to
form (gab junctions)
•through which ions can flow freely
between individual muscle cells.
•Therefore, it functions in a syncytial
fashion, as in cardiac muscle.
•Visceral smooth muscle is not under
voluntary control, and a major share of its
control is exerted by non-nervous stimuli
(hormonal, chemical and stretch).
THE SMOOTH MUSCLE:
Multiunit smooth muscle :
•Multiunit smooth muscle is made up of
individual, discrete muscle units without
interconnecting bridges.
•Each fiber contracts independently of
the others and is often innervated by a
single nerve ending; yet, it is not under
voluntary control.
•Another important characteristic of
these muscles is that their control is
exerted mainly by nerve signals,
•found in structures in which fine graded
contractions occur, e.g the ciliary muscle
and iris muscle of the eye, as well as the
piloerector muscles.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity
• It is characterized by the instability of its
membrane potential. Thus, its membrane
potential has no “resting” value;
• yet, in periods between increased and
decreased activity, it averages (–50 mV).
• Superimposed on this membrane potential
are slow, sine wave-like fluctuations
(oscillations) a few mVs in magnitude, e.g
visceral smooth muscle of the gut.
• Slow waves themselves are not APs, but can
initiate APs when peak of the negative
wave reaches about (–35 mV),
level).
(firing
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity
• APs of the visceral smooth
muscles occur in one of the
following:
1) spike potentials or
2) APs with plateaus.
• The pacemaker potentials are
generated in multiple foci shifting
from one place to another
• They are conducted for some
distance,
controlling
the
rhythmical
contractions
(peristalsis) of the gut.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity
• Typical spike potentials may occur on
the rising or falling phases of the
oscillations.
• Spike potentials are of short duration
(10–50 ms) and can be elicited by
•
•
•
•
•
electrical stimulation,
by hormones,
by transmitter substances from nerve fibers,
by stretch or
spontaneously generated in the muscle fiber
itself.
• On the other hand, APs have a
prolonged plateau phase just like in
cardiac muscle.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Electrical and Mechanical Activity
• In unitary smooth muscle, the
repolarization is delayed for several
hundred milliseconds to 1 second.
• The importance of the plateau is that it
accounts for the prolonged contractions
in some types of smooth muscles like
the ureter, the uterus under some
conditions and vascular smooth muscle.
• As a result, visceral smooth muscle
shows a continuous maintained state of
irregular partial contractions that are
independent of its nerve supply and are
called tonus or tone of the muscle.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Molecular Basis of Contraction:
• Visceral smooth muscle starts to contract
about (200 ms) after the start of the spike
potential, and the peak contraction about
(500 ms) after the spike.
• Thus, the excitation-contraction coupling is
a very slow process.
Remember; in skeletal and cardiac
muscle, time from initial depolarization to
initiation of contraction is <10 ms.
• Ca+2 is involved in the initiation of
contraction of the smooth muscle.
• The myosin in the smooth muscle must be
phosphorylated for the activation of myosin
ATPase activity that will cause the power
stroke.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Molecular Basis of Contraction:
• Being a slow muscle, the time that the
cross-bridges remain attached to actin
filaments is greatly increased,
• causing a greater maximum force of
contraction.
• A possible reason for the slow cycling is
because of far less myosin ATPase activity
than in skeletal muscles.
• Instead, Ca+2 binds to calmodulin protein
and the resulting Ca+2-calmodulin complex
activates the enzyme myosin kinase
• This enzyme catalyzes the phosphorylation
and activation of myosin ATPase, causing
contraction.
THE SMOOTH MUSCLE:
Unitary (Visceral) smooth muscle : Molecular Basis of Contraction:
• Relaxation of visceral smooth muscle
occurs when Ca+2 ion concentration falls
below a critical level, causing
dissociation of Ca+2-calmodulin complex.
• Contractile processes are reversed,
except for the phosphorylation of the
myosin head which requires another
enzyme, myosin phosphatase.
• This enzyme splits the phosphate from
myosin, then cross-bridge cycling stops
and contraction ceases.
Latch Bridge Mechanism :
•Here, myosin cross-bridges remain attached to actin for
sometime after decreased Ca+2 concentration. This mechanism
produces sustained contraction with little expenditure of
energy.
•Once developed full contraction, the amount of excitation
usually can be reduced to far less the initial level and the
energy consumed to maintain contraction is often very small.
•The importance of the latch bridge mechanism is that it can
maintain prolonged tonic contractions for hours or days.
•Especially important in vascular smooth muscle to maintain
the blood pressure. In addition to organs such as the intestine,
urinary bladder and gallbladder often maintain tonic muscle
contraction almost indefinitely.
R e l a t i o n o f L e n g t h t o Te n s i o n
Plasticity
•It is the variability of the tension the smooth muscle
exerts at any given length.
•If a piece of visceral smooth muscle is stretched, it
first exerts increased tension, however, the tension
gradually decreased after a while.
•It is, therefore, impossible to correlate length to
developed tension accurately, and no resting length
can be assigned.
•The consequences of plasticity can be demonstrated
in intact human urinary bladder.
THE SMOOTH MUSCLE:
Stimulation:
• Visceral smooth muscle contracts when stretched in
the absence of any extrinsic innervation: There will be
- a decline in the membrane potential (less negative).
- an increase in the frequency of the spikes.
- a general increase in muscle tone.
• If catecholamines (epinephrine and norepinephrine)
added to a preparation of intestinal smooth muscle:
- the membrane potential usually becomes larger (more negative).
- the spikes decrease in frequency.
- the muscle relaxes (decreased tone).
• Normally, stimulation of noradrenergic nerves to the
intestine inhibits intestinal contraction in vivo.
THE SMOOTH MUSCLE:
Stimulation:
• Acetylcholine has an effect opposite to that of norepinephrine
on the membrane potential and the contractile activity of
intestinal smooth muscle:
- the membrane potential decreases (more positive).
- the spikes become more frequent.
- the muscle becomes more active with an increase in tonic tension and the
number of rhythmic contractions.
• In the intact animal (in vivo), stimulation of cholinergic nerves
causes excitatory potentials and increased intestinal
contractions.
• In vitro, similar effects are produced by cold and stretch.