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Transcript
Smooth muscle physiology
Organizational structure & function
Excitation contraction coupling
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle anatomy
• Smooth muscle is considered to be much
more primitive than either cardiac or skeletal
muscle.
• Muscle striations are not visible in smooth
muscle, so the sarcomere relationship of
myosin to actin does not exists in smooth
muscle.
• However, per cross sectional area smooth
muscle is as strong as skeletal muscle and
smooth muscle is highly resistant to fatigue.
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Anatomy
• I. Smooth Muscle
• 1. Fibers are smaller than skeletal muscle
• 2. Involuntary (Usually)
• 3. No apparent myofibrils under the light
microscope - No cross striations
• 4. Fibers are thickest in the middle and have
tapered ends
• 5. Centrally located single oval nucleus
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle anatomy
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle anatomy
• 6. Sarcoplasm contains thick and thin filaments
• a. Not in an orderly pattern
• b. there are 10 – 20 times more thin filaments
than thick filaments
• 7. Dense bodies
• a. Have thin filaments attached to them
• b. Function is similar to Z disks
• c. Dispersed throughout the sarcoplasm or
attached to the sarcolemma
• d. Thin filaments stretch from one dense body
to another
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Anatomy
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle anatomy
• B. Generation of Contraction
• 1. Sliding filament mechanism involving thick and
thin filaments generates tension that is transmitted
to the thin filaments
• 2. Does not contain Troponin complex
• 3. Actin and myosin pull on the dense bodies
attached to the sarcolemma
• 4. Shortening of the smooth muscle fiber is
lengthwise, the middle of the fiber thickens
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Anatomy
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Anatomy
• 5. Shortening causes bubble like
expansion of the sarcolemma
• 6. Shortening is corkscrew like - the fiber
twists in a helix as it shortens and rotates
in the opposite direction as it lengthens
Copyright © 2010 Pearson Education, Inc.
Types of smooth muscles
• Single Unit - Large
aggregates of smooth
muscle cells which act
as a single unit.
• Multi Unit - Single
smooth muscle cells
usually with a single
nerve connection
Copyright © 2010 Pearson Education, Inc.
Types of smooth muscles
Copyright © 2010 Pearson Education, Inc.
Types of smooth muscles
• A. Multi-unit smooth muscle
• Composed of discrete,separate smooth muscle fibers
• Each fiber operate/contract independently of others
• Often innerveted by a single nerve ending as occurs for
skeletal muscles
• Their control is exerted mainly by the nerve signals
• Outer surface are Covered by a thin layer of basement
membrane of fine collagen and glycoprotein fibrillae that
help to insulate the separate fibers from one another
• Examples: the ciliary & iris muscles of the eye; the piloerector
muscles that cause erection of the hairs when stimulated by the
sympathetic nervous system
Copyright © 2010 Pearson Education, Inc.
Types of smooth muscles
B. Single Unit - Unitary Smooth Muscle - (Syncytial smooth
muscle or visceral smooth muscle)
• Is a mass of hundreds to thousands of smooth muscle
fibers that contract as a single unit
• The fibers are aranged in sheets or bundles and their cell
membranes are adherent to one another at multiple points
so that force generated in one muscle fiber can be
transmitted to the next
• The cell membranes are joined by many gap junctions
through which ions flow freely from one muscle cell to the
next so that action potentials or simple ion flow without ion
potentials can travel from one fiber to the next and cause
muscle fibers to contract together
Copyright © 2010 Pearson Education, Inc.
Types of Smooth Muscle
• Response to different types of stimuli
• Nerves, hormones, mechanical stretch, endothelial
mediators (EDNO)
• Location
• Form part of the walls of both large and small
arteries and veins
• Hollow viscera - Stomach, intestines, uterus,
urinary bladder,bile ducts etc
• Muscle forms large networks and an action
potential causes contraction of the entire organ
Copyright © 2010 Pearson Education, Inc.
• Function
• Control the size of organs
• cause the release of substances
• Control the rate of flow (blood, contents of GI tract,
urine) - etc.
Copyright © 2010 Pearson Education, Inc.
Multi vs. Single-Unit Muscle
Copyright © 2010 Pearson Education, Inc.
comparison of smooth muscle contraction
& skeletal muscle contraction
• Most skeletal muscles contract and relax rapidly as
compared to Most smooth muscle contraction which is
prolonged tonic contraction sometimes lasting hours or
even days
• This is caused by their differences in chemical and
physical properties
1. Slow cycling of the myosin cross bridges
2. Low energy requirement to sustain smooth muscle
contraction
3. Slowness of onset of contraction and relaxation of the
total smooth muscle tissue
4. Maximum force of contraction is often greater in
Copyright © 2010 Pearson Education, Inc.
comparison of smooth muscle contraction
& skeletal muscle contraction
5. Latch Mechanism - prolonged holding in smooth muscle
• After contraction is initiated, less stimulus and energy
are needed to maintain the contraction (Energy
conservation)
• Can maintain prolonged tonic contractions for hours with
little energy and little excitatory signal from nerves or
hormones
• Mechanism: lower activation of enzymes, myosin head
remains attached to actin for long periods of time but
large numbers are attached and the force is great
Copyright © 2010 Pearson Education, Inc.
comparison of smooth muscle contraction
& skeletal muscle contraction
6. Stress - Relaxation of Smooth Muscle
• Important characteristic of visceral smooth muscle
• Stress - Relaxation response - ability to return nearly
to its original force of contraction seconds or minutes
after it has been elongated or shortened
• When smooth muscle is initially stretched - it will
contract and increase tension (Myogenic
response)
• Smooth muscle fibers can stretch and still
maintain their contractile function
Copyright © 2010 Pearson Education, Inc.
comparison of smooth muscle contraction
& skeletal muscle contraction
• Smooth muscle can undergo great changes in
length and still retain the ability to contract
effectively
• This response allows vessels and hollow
organs to change size but maintain the
pressure within the structure at a constant
level (Probably related to the “latch
mechanism”)
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Contractile Mechanism
• Contractile Process in Smooth Muscle
• 1. Chemical basis for smooth muscle contraction
• a. Contains actin and myosin filaments similar in
structure and interaction to skeletal muscle
• b. No troponin complex - mechanism for contraction
is different
• c. Calcium influx activates the contractile process
• d. ATP provides energy for contraction
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Contractile Mechanism
• Regulation of Contraction by Calcium Ions
• ICF calcium is the initiating event for smooth
muscle contraction
• An increase in calcium influx can be caused by:
• nerve stimulation
• Hormones
• chemical changes in the environment (Ligands)
• mechanical stretch of the fiber
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Contractile Mechanism
• Role of calmodulin in excitationcontraction-coupling in smooth muscle
• a. Smooth muscle has no Troponin but it does
have a regulatory protein called calmodulin
• b. Calmodulin is similar in structure to
Troponin and like Troponin combines with 4
calcium ions causing activation
• c. Activated calmodulin-Ca++ complex
activates myosin light chain kinase
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Contractile Mechanism
• d. The activated myosin light chain kinase
phosphorylates the myosin light chains (regulatory
proteins on the myosin heads) using an ATP unit
• e. The myosin heads now engage actin and cross
bridge cycling proceeds using the same process as
in skeletal muscle
• f. Cessation of contraction
• 1. As [Ca++] drops below a critical level
• 2. Myosin phosphatase removes the phosphate
from the myosin light chains and contraction stops
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Cell
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Contraction: Mechanism
Copyright © 2010 Pearson Education, Inc.
Smooth Muscle Relaxation: Mechanism
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
• Smooth muscle responds to stimulation from
a number of different physiological systems.
• 1. Nerves
• 2. Hormones
• 3. Mechanical manipulation
• 4. Self stimulation (Automaticity)
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE
Neural-Muscular Junction
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
• Excitatory and inhibitory transmitter
substances at NMJ
• a. Ach & norepinephrine are never secreted by the
same nerve fiber
• b. Ach can be excitatory or inhibitory - determined
by the type of receptor expressed by the target cell
• c. Ach and NE usually cause the opposite reaction
at a target cell (If Ach is stimulatory then NE will
most likely be inhibitory)
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
Unitary
• Membrane Potential and AP in smooth muscle
(Slow waves and Spike Potentials)
• Unitary smooth muscle
• a. Slow waves - In smooth muscle the resting
membrane potential is variable - usually about -50
to -60 mV
• b. Variable resting membrane potential is called
the basic electrical rhythm or BER or sometimes
slow waves
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
Unitary
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
Unitary
• Slow waves and spontaneous generation of
action potentials
• 1. Slow waves are not action potentials - they are
local unstable resting membrane potential and
they determine the rhythmicity of smooth muscle
contractions
• 2. Slow waves can initiate true action potentials
called spike potentials (Ca++ voltage gated)
• 3. Spike potentials are generated whenever BER
exceeds threshold about -35 mV
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
Unitary
• Spike Potentials
• a) Spike potentials cause rhythmic
contractions of smooth muscle
• b) Increase the number of spike potentials
and increase the force of smooth muscle
contraction
• c) Regulation - mechanical stretch, hormones,
and Ach cause membrane to become less
negative (Hypopolarize the cells)
Copyright © 2010 Pearson Education, Inc.
SMOOTH MUSCLE STIMULATION
Unitary
Copyright © 2010 Pearson Education, Inc.
Depolarization of Multiunit
Smooth Muscle w/o AP
• Smooth muscle contraction in response to local
tissue factors
• 1) Arterioles, metarterioles & precapillary sphincters
have little or no nerve supply
• 2) Highly contractile smooth muscle responds
rapidly to local factors
• Lack or a decrease in O2 levels - Increase in CO2
- Increase in hydrogen ions - Decrease in ECF
Ca++ - Adenosine or increased lactic acid –
Cause Vasodilation
Copyright © 2010 Pearson Education, Inc.
Depolarization of Multiunit
Smooth Muscle w/o AP
• Effect of hormones on smooth muscle contraction
• 1) Most hormones affect smooth muscle through
second messengers
• 2) Important hormones - Norepinephrine,
epinephrine, Ach, angiotensin II, oxytocin,
vasopressin, serotonin and histamine
• 3) Action of hormones is controlled by the type of
receptors expressed by the target cell - hormone
(Ligand) gated excitatory and inhibitory receptors
(Ca++ or K+ channels)
Copyright © 2010 Pearson Education, Inc.
Comparisons Among Skeletal,
Smooth, and Cardiac Muscle
Copyright © 2010 Pearson Education, Inc.