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Smooth and Cardiac Muscle
Lanny Shulman, O.D., Ph.D.
University of Houston College of
Optometry
Smooth Muscle Found in:
• Sheets lining walls of hollow viscera
(i.e. gastrointestinal tract)
• Attached to hair follicles
• Blood Vessels
Major Function:
• Movement of viscera
• Peristalsis
• Vasoconstriction
Distinguished from Other Muscle Tissues
(Structural Differences):
• Small spindle shaped fibers (2-5µm x
400 µm)
• Single Nucleus
• Lacks Cross-striations, Z Lines,
myofibrils, sarcomeres
• Dense Bodies
• Actions are involuntary
• Contain tropomyosin but no troponin
• Poorly developed sarcoplamic
reticulum
Structural Differences cont.:
• Gap Junctions between fibers
• Intermediate Filaments (Desmin,
Vimentin)
• Few mitochondria—low ATP
consumption
• Relies mainly on aerobic glycolysis for
metabolic needs
• Caveolae
Functional Differences:
• Ca2+ ions trigger contractions through a
different mechanism than that found in
other muscle types.
• Most Ca2+ ions that trigger contractions
enter the cell from the extracellular
fluid.
• Cells are able to contract over a greater
range of lengths than skeletal or
cardiac muscle because actin and
myosin filaments are not rigidly
organized.
Functional Differences cont.:
• Autonomic innervation
– Excitatory & inhibitory
– Sympathetic & parasympathetic
– Norepinephrine, Acetylcholine
– No specialized endplate region
– Multiple varicosities
• Hormonal control
• Automaticity
Electrical Coupling
• Single Unit
– Found in walls of hollow organs (stomach,
bladder, esophagus)
– Contract rhythmically as spontaneous
waves of contractions
– Occur in large sheets
– Low resistant bridges between individual
cells—Gap Junctions
– Function in a syncytial fashion
– Has neuromuscular junctions that serve a
bundle of muscle fibers
– Slow; no AP
Electrical Coupling
• Multi-unit
– Iris, large arteries, veins
– Continuously active (sphincters, walls of
blood vessels, sphincter and dilator
muscles of eye)
– Made up of individual units without
connecting bridges-no Gap Junctions
– Regulation of individual cells
– Fine, graded contractions occur (eye)
Contractile Responses
• Tonic
– Long forceful contraction
– Constant Tone (latched)-no AP
– BV walls, airways, many sphincters
• Phasic
– Typically not constricted
– Intermittent forceful contractions-AP
– GI, Urinary, Reproductive tissues, large
arteries
Calcium and Smooth Muscle
• Regulates Cross-Bridge Cycling
• Indirect role due to the absence of
troponin
• Ca2+ acts on the cross-bridge itself
• Involves phosphorylation at a specific
serine residue on the light chain
• Uses ATP as a phosphate donor
Calcium Mobilization
• Phasic Contraction:
1. Single brief stimulus elicits transient
increase in Ca2+ and small contraction
(solid lines)
2. Repeated stimuli lead to transient
increases and decreases in Ca2+ and
summation of contractions (dotted
lines).
•
Tonic Contractions:
1. Initial Ca2+ release from sarcoplamic
reticulum induces rapid force
development (solid lines). However,
peak [Ca2+] is not maintained but
remains above threshold until
stimulus is removed.
2. If Ca2+ is blocked from SR (dashed
lines), the contraction is much slower.
Mechanisms Regulating
Myoplasmic [Ca++]
1. Membrane potential-dependent Ca++ influx
through Ca++ channels from extracellular
space
2. Receptor-activated Ca++ channels in the
sarcolemma
3. Control of Ca++ release from the
sarcoplasmic reticulum
4. Sequestration and extrusion of Ca++ by
pumps in both membranes
5. Na+- Ca++ exchange across the sarcolemma
Molecular Basis of Contraction
1.
2.
3.
4.
5.
6.
Intracelluar calcium levels rise to trigger
contraction
Ca2+ binds calmodulin (4:1).
The active Ca2+-calmodulin-MLCK complex
phosphorylates a serine residue on the myosin
light chains associated with each myosin head.
This phosphorylation requires one ATP.
Fast cross-bridge cycling in smooth muscle. The
release of ADP and Pi generates the power stroke.
The conformation of the myosin head changes
from 90o to 45o.
This cycling requires a second ATP to bind the
myosin head, to hydrolyze ATP to myosin-ADP-P,
to release the myosin from actin, and reset the
myosin head to a high potential energy 90o angle.
Myosin light chain phosphatase is continually
removing the phosphates put on myosin light
chains by active MLCK.
Model of the Latch State:
• Special state that allows smooth
muscle to maintain tone with minimal
expenditure of ATP.
• Myosin cross-bridges remain attached
to actin after [Ca2+]i falls.
• Produces sustained contraction with
little expenditure of energy.
Latch State Model cont.
• If myosin light chains are
dephosphorylated, ATPase activity
decreases.
• Myosin heads continue to hold force at
muscle ends.
• Low myosin ATPase activity probably
exists even after dephosphorylation.
Smooth Muscles of the Eye and
Adnexa
• Tarsal or Müller’s Muscle of the eyelid
– Function: elevates upper lid, depresses lower lid
– Innervation: sympathetic nervous system
• Dilator muscle of the iris
– Function: dilate the pupil (mydriasis)
– Innervation: sympathetic nervous system
• Sphincter muscle of the iris
– Function: constrict the pupil (miosis)
– Innervation: parasympathetic nervous system
• Ciliary Muscle of the ciliary body
– Function: accommodation (focus from distance to near)
– Innervation: parasympathetic nervous system
Cardiac Muscle
• Found in the wall of the heart
• Function is to pump blood to the body
and maintain blood pressure
• Cardiac cells are small with one central
nucleus
• Mechanism of contraction is similar to
slow skeletal muscle
• Cells are striated and joined end to end,
forming fibers
• Intercalated Discs & Gap Junctions
• Cisternae are less well developed &
store less Ca2+ than skeletal muscle
• Extra Ca2+ is released from transverse
tubules causing twitches to be 10x
longer than skeletal muscle twitches
• Energy needs are met by aerobic
metabolism thus cells contain many
mitochondria
• Functions as a syncytium
• Automaticity
• Pacemaker cells
Intercalated Discs
• Gap Junctions
• Desmosomes (maculae adherens)
• Fasciae adherens
Electrical Properties
• In mammalian hearts, depolarization
lasts ~ 2 ms.
• Plateau phase and repolarization lasts
200 ms or more.
• Repolarization is not complete until
contraction is half over
Phases of Action Potentials
• Depolarization and overshoot are due to opening
of voltage-gated Na+ channels (phase 0) . Na+
influx
• The initial rapid repolarization (phase 1) is due to
closure of the Na+ channels. No Na+ influx
• The prolonged plateau is due to opening of
voltage-gated Ca++ channels (phase 2). Ca++ influx
• Repolarization to the resting potential (phase 3) is
due to closure of the Ca++ channels and efflux of
K+ through K+ channels.
Ion Channels
• Na+ channels: 2 gates; outer gate that opens
at start of depolarization (-70 to -80 mV);
inner gate that closes and stops influx of Na+
until AP is over.
• Ca++ channels: activated at -30 to -40 mV
• K+ channels: 3 types
(1) ITO : early incomplete repolarization
(2) IKr : at plateau potentials: allows K+ influx
but resists K+ efflux
(3) IKs : outward current; sum of IKr & IKs is
small outward current that increases with
time and repolarizes
Mechanical Properties
• Repolarization time decreases as cardiac
rate increases.
• Contractile response begins just after start of
depolarization and lasts 1.5x as long as AP.
• Skeletal muscle: release of [Ca2+]o due to
depolarization
• Cardiac muscle: release of [Ca2+]o due to
activation of dihydropyridine channels
• Absolute refractory period: Phases 0-2 and
half of phase 3 ∴ tetanus is not possible
Spontaneous Contraction Versus
Neural Control
1.
•
•
•
2.
•
•
•
•
Purkinje Cells (cardiac conducting cells)
Modified cardiac muscle cells
Organized into nodes and bundles
Transmit contractile impulse
Unmylinated nerves
Derived from vagus nerve (CN X)
End near the nodes
Do not initiate contraction
Modify the rate of muscle contraction
Injury and Repair
• Mature cardiac cells do not divide
• Injured cardiac muscle tissue is
repaired by the formation of fibrous
connective tissue
• Loss of cardiac function at site of injury
• This is pattern of injury and repair in
non-fatal myocardial infarction