8. Smooth Muscle Histology and Physiology Flashcards

1
Q
• Locations:
– Wall of \_\_\_\_ organs, blood vessels, \_\_\_\_ of the eye, \_\_\_\_
muscle of the hair follicles.
• Regulation of the internal environment: e.g. movement of fluids, air. 
• Capable of \_\_\_\_ and \_\_\_\_.
• Very economical in energy terms.
• Involuntary control:
– \_\_\_\_ system.
 – Circulating \_\_\_\_.
– \_\_\_\_ hormones.

• Multiple arrangements:
– ____
– ____
– ____

A

tubular
iris and ciliary body
piloerector

contraction
relaxation

autonomous
hormones
local

sheets
rings
bundles

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2
Q

III. Smooth Muscle

Unique to smooth: capable of contraction and relaxation; striated muscle is always referred to by contraction, only relaxes once stimulation is eliminated; smooth muscle has ____ (neural/hormonal) that induce a contraction (similar to skeletal muscle), and there are modulators that induce ____

Steady state of smooth muscle = always ____ (mechanisms to induce relaxation smooth muscle, different from skeletal)

Smooth muscle uses little energy when compared to skeletal muscle (binding actin to myosin, and myosin in smooth muscle has a low rate of ATPase-activity [____ lower]) > contraction is much ____ than skeletal, but very ____

A

regulators
relaxation

contracted

100-fold
slower
cheap

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3
Q

Smooth Muscle Histology

 • The smooth muscle cell:
• Small: average length = \_\_\_\_ μm.
• Fusiform with a \_\_\_\_ nucleus.
• not \_\_\_\_.
• \_\_\_\_ instead of Z disks.
• Ionic connections between cells through
gap junctions: \_\_\_\_.

Cell that is nothing like skeletal/striated muscle > these cells can be confused with connective tissue cells = ____; similar phenotype: small (similar to euk cell in mammals)

Cytoplasm has no indication of ____

Highly interconnected (both mechanical and electrical connections) > induced to contract and relax as a single functional unit, in a coordinated manner

Each cell has one nucleus, but the ____ acts sintitially (due to the nature of their mechincal/electrical connections)

A
50-500
single central
striatied
dense bodies
functional syncytium

fibroblasts
sarcomeres
organ

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4
Q

The Smooth Muscle Cell

  • No ____ system.
  • Instead of T tubules → ____:
  • Invaginations of the sarcolemma:
  • ↑ ____ → ↑ Ca2+ transport.
  • Associated with the ____.
  • Sarcoplasmic reticulum:
  • Poorly ____.
  • Organized in tubes or sheets.
  • Myofilaments:
  • Thick ____ (slow myosin) filaments.
  • Thin ____ filaments.
  • Intermediate filaments (desmin, vimentin).
  • Cytoplasmic and plasma membrane dense bodies (α-actinin):
  • Functionally similar to ____.
  • Attachment of actin and intermediate filaments.
  • Cell connections:
  • Mechanical: through ____
  • Electrical: through gap junctions - ____.
  • ____ surrounding each SMC.
A

T tubules
caveolae
surface area
SR

developed
myosin
actin

Z disks

desmosomes
funtional syncytium
basal lamina

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5
Q

The Smooth Muscle Cell

No sarcomeres

Caveolae > increase ____ > enrichment in receptors involved with modulation, and in calcium channels

SR in smooth is morphologically identical to a ____ (like in fibroblasts)

Myofilaments are not bound to Z-disks > dense bodies (two types): ____ dense bodies, and ____ dense bodies > built by same protein as Z disk, but structure is very different

Electrical connection > flow of ions, ions traffick from one cell to the next thereby transmitting the contractile impulse

Mechanical connection > ensures that cells that are tightly attached will be pushed/pulled > ____ of smooth muscle fiber

____ is produced by smooth muscle cell

A

SA
regular ER
PM
cytoplasmic

coordinated
basal lamina

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6
Q

Smooth Muscle Histology

Longitudinal > ____ nuclei

Cross > the tissue is not different from connective tissue in what they produce [???] (elastin, etc.) but can uniquely be stimulated

A

centrally located

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7
Q

Structural Arrangements of SM Fibers: Circular Organization

  • Typical of ____ and ____.
  • Partially contracted at all times: ____.
  • Vasoconstriction: additional contraction, which ____ the diameter of the vessel lumen.
  • Vasodilation: relaxation, which ____ the diameter of the vessel lumen.

Circular organization > BV and airways > muscle cells are partially contracted at all times, the vessel is never completely relaxed > the ____: partially contracted, or muscle tone/tonicity

From this basal state > BV can be induced to contract > vasoconstriction > modulators increase contraction and diameter is reduced

Other modulators that induce vasodilation, opening the lumen of vessel/airway by relaxing the SMC

A

BV
airways
muscle tone

narrows
widens

steady state

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8
Q

Structural Arrangements of SM Fibers: Circular and Longitudinal Organization

• Typical of GI tract organs: e.g. ____ and ____ intestines.

  • Two layers:
  • Outer: ____.
  • SM fibers run parallel to organ’s long axis.
  • Contraction: organ ____.

• Inner: ____.
• SM fibers run around circumference of
organ.
• Contraction: organ ____

• Both layers coordinate contractions and relaxations: ____ movements.

A

small
large

longitudinal
shortening

circular
elongation

peristaltic

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9
Q

The Smooth Muscle Neuromuscular Junctions

• Very different from the skeletal muscle NMJ.

  • Two types:
  • Unitary NMJ:
  • Hundreds to millions of muscle cells act as a functional unit.

• SMCs mechanically connected by desmosomes and electrically connected by gap junctions.

  • Autonomic nerve cells do not make ____ with the SMCs: ____ junctions:
  • Release of neurotransmitters into the ECM at some ____ from the cells: diffusion to reach target SMCs.
  • Neurotransmitter released from ____: enlargements on the axon.
  • E.g. ____ wall, ____ and many blood vessels.

Unitary > innervated by a ____ from the autonomous NS (functional unit), but it is not in direct contact with any of the cells > releases NTs from specialized structures > and disperse to the entire FU and they are induced to contract; all these cells are also connected via gap junctions and the diffusion spread via gap junction

SMC REACT TO TWO STIMULI: direct binding to ____, and the ____ between cells > result: contract/relax in a coordinated matter

A
direct contact
diffuse
distance
varicosities
gastrointestinal
uterus

single neural termination
receptors
electrical gap junction

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10
Q

The SM Neuromuscular Junctions

Multiunit NMJ:
Each SMC is innervated ____: low cell- to-cell communication.

Nerve cell varicosities make ____ contact with the target SMCs: ____ junctions.
E.g. ____ muscle of the hair follicle, the ____ and ____ muscles of the eye.

The contact between neuron and cell is in direct contact but not as ____ as skeletal muscle

A
independently
direct
contact
piloerector
iris
ciliary

intimate

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11
Q

Contraction and Excitation of Smooth Muscle

• SM contracts or relaxes in response to nerves and stimuli (striated muscle can only ____).

• Numerous possible inputs to contract or relax smooth muscle:
a. ____ nerves.
b. Circulating hormones: e.g. angiotensin, vasopressin.
c. ____ hormones (or paracrines): e.g. histamine, somatostatin, and
endothelin [potent vasoconstrictor]).
d. Ions and metabolites: e.g. O2 , CO2.
e. ____ from other cells: e.g. NO.
f. Signals from electrically-coupled SMCs.
g. ____ cues: e.g. stretch.

A
contract
autonomic
local
signals
mechanical
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12
Q

Contraction and Excitation of SM: Neuromuscular Transmission

Neuromuscular transmission in SM:
• ____ process (up to minutes).
• Commonly modulates ____
rhythmic activity.

Contraction/relaxation of smooth muscle can be initiated by:

  1. Intrinsic activity of ____ cells.
  2. Neural transmitters.
  3. Circulating or locally generated hormones or signaling molecules.

Multiunit muscles:
• No ____.
• ____ is most important.

Single unit muscles:
• ____ is propagated throughout the tissue.

Phasic contraction/relaxation > generate peristaltic movements [???}

Smooth muscle present in tissues that contain specialized cells (may not be ____) > that may regulate the pace of contraction

A

slow
spontaneous

pacemaker
electrical coupling
neural regulation

electrical activity

smooth muscle

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13
Q

Contraction and Excitation of Smooth Muscle: Membrane potentials

Resting Vm: -50 mV, (~ ____ higher than in skeletal muscle).

A. Spike potentials:
• Similar to those in skeletal muscle.
• Triggered by nerve stimulation, stretch or hormones; also
____.
• Single twitch or larger summed ____ responses.
• Characteristic of single-unit SM (e.g. ____).
• Gap junctions permit the spread of action potentials
throughout the tissue.

Much more negative potential in skeletal muscle cells

A

30
spontaneously
mechanical
visceral SM

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14
Q

Contraction and Excitation of Smooth Muscle: Membrane potentials

B. Slow waves:
• Rhythmic activity that may trigger action potentials.
• Not ____: fluctuations in membrane
potential from the activity of ____
(e.g. ____) in the cell membrane.
• Typical of the intestinal wall: important in ____.

Slow waves > ____, internal change in membrane potential due to variations in pumps working (pumping different rates at different times)

Sometimes the potential can be so depolarized that it is enough to cross the threshold and create an AP (NT has to induce traffic of ions, and if it is above threshold, more ions would enter and the depolarization would be even higher)

Cells contract ____ by themselves; waves are not AP, but sometimes the depolarization is so high that it induces the formation of an AP

A

action potentials
electrogenic umps
Na+/K+ ATPase
peristalsis

innate

spontaneously

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15
Q

Contraction and Excitation of SM: Membrane potentials

C. Graded changes in membrane potential:
____ contractile activity related to membrane potential in the absence of action potentials. Common in ____ (e.g., vasculature).

Never a creation in ____ > change in membrane potential > some degree of contraction/relaxation > variations in amount of ____, without the need to generate an AP

A

tonic
multiunit SM
AP
contractile force

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16
Q

Contraction and Excitation of Smooth Muscle: Membrane potentials

D. Action potential with plateau:
• Organs such as the ____.
• After rapid depolarization, repolarization is ____
by as much as 1 sec (SM remains contracted).
• A similar type of action potential occurs in ____.

____ stimulus to contract cell > very rapid depolarization (real AP); but the repolarization is delayed by up to a second > during this time there is a contractile force created without the need to repeat the stimulus

A

uterus
delayed
cardiac muscle

single

17
Q

Smooth Muscle Physiology: Contractile Mechanism

  • Different mechanism to striated muscle:
  • Actin and myosin filaments not organized in ____.
  • Shortening occurs between ____.
  • Cell balloons out between ____ points.
  • SM myosin ATPase activity is more than ____ lower than that of fast skeletal muscle myosin.
  • SM can generate higher ____ and can ____ more than skeletal muscles (up to ____ of their resting length compared to ____ in skeletal muscles).
A
sarcomeres
dense bodies
dense body anchor
100-fold
tension
contract
30%
65%
18
Q

Smooth Muscle Physiology: Contractile Mechanism

SMC fibers are connected electrically and mechanically > bt cells there are desmosomes, and ECM fibers (connective, not made by connective tissue but by ____) > connect cells mechanically (collagen, fibronectin, elastin and connected to integrins at level of PM), and also these molecules provide ____ to over stretching by collagen and ____ by elastin, and helps to maintain ____ by collagen, and conserve ____ during relaxation process by accumulating recoil energy from elastin helping the relaxation of the whole tissue

A
SMC
resistance
recoil
structure
energy
19
Q

Excitation-Contraction Coupling in SM Cells: Liberation of Ca2+

• ____ is required for myofilament contraction.
• Ca2+ must be liberated from:
– Internal stores in the ____.
– External supply via ____ in the sarcolemma:
• ____ Ca2+ channels.
• ____ Ca2+ channels: independent of membrane depolarization.
• NO ____ in Smooth Muscle Cells.
• Major routes of Ca2+ entry and exit from
SM cytoplasm:

– Left: ↑[Ca2+] → contraction.
– Right: ↓[Ca2+] → relaxation

Calcium is required; not only liberated from SR stores, but most is imported from the ____

Voltage-gated channels (change in the polarization of the membrane will induce to open), and some are ligand-gated channel (not responding to AP, a ____ or GF though)

A
Ca++
SR
channels
voltage-gated
ligand-gated
T tubules
EC matrix
hormone
20
Q

Smooth Muscle Contraction: Activation of MLC

In striated > Ca++ modifies troponin > tropomyosin, moves into groove of thin filament > now head of myosin can bind actin

inactive myosin > ____ protein chains (two HC w/ ____, and two LC w/ ____)

In smooth > Ca++ binds ____, this complex > ____ > transfers phosphate to ____ region

A
four
ATPase domain
regulatory domain
calmodulin
MLCK
LC regulatory
21
Q

Smooth Muscle Contraction: Activation of Myosin Light Chains
(MLCK)

Since Ca2+ control in smooth muscle is at the ____ filaments:
____ regulation

Inactive state > myosin tail is ____

Upon binding phosphate, the tail of myosin changes conformation (release of myosin tail) > active state > open ____ site on the head of the myosin HC > ____ (similar to striated muscle)

Control in striated was at thin cell > ____ regulation

Control in smooth is at thick cell > ____ regulation

A

thick
myosin-linked

disordered

actin-binding

bipolar filaments

actin-linked
myosin-linked

22
Q

Smooth Muscle Contraction: Cross-bridge Cycle

  • ATP is needed at ____ different points:
  • One ATP to phosphorylate ____.
  • One ATP per cycle of the ____.
  • SM myosin ATPase activity is >100-fold lower than in striated muscle: ____ contraction.
  • Phosphorylated cross-bridges cycle until myosin is dephosphorylated by a ____.

MLCK transfers phosphate to LC of myosin regulatory region > activated > can bind actin filaments > high-affinity for actin when domain is bound to ADP/Pi from previous cycle > power-stroke after release of both ADP/Pi > ATPase domain increases affinity for ATP and binds it thus releasing from thin filaments > hydrolyzes ATP, and prepares for the next cycle

Smooth muscle difference form striated > ____ > removes phosphate group that was added by MLCK; when active, eliminates phosphate, and myosin cannot bind actin (reverts back into inactive, disordered tail state)

In striated, did not need ____ to phosphorylate myosin

A
two
myosin
cross-bridge
slow
myosin LC phosphatase (MLCP)

myosin phosphatase
ATP

23
Q

Contraction and Excitation of Smooth Muscle: The Latch State

• Latch state (or latch bridge):
• At full contraction, part of the phosphorylated
myosin is dephosphorylated by myosin light chain
phosphatase.
• Dephosphorylated myosin does not ____ from actin.
• SM stays contracted even though cross-bridge
cycling of dephosphorylated myosin molecules
does not occur (and no ATP is used).
• The latch bridge helps to maintain ____
with minimal ATP consumption.

A

immediately detach

muscular tone

24
Q

The Latch State
• Myosin gets dephosphorylated by myosin phosphatase

  • Myosin and actin remain attached
  • ____ maintained
  • No ____ needed
  • Minimal energy utilization

Latch-state > ____ not increasing nor disappearing

Very cheap way of maintaining tone > doesn’t need to go through cross-bridge in order to maintain contraction

A

tone
ATP
contraction

25
Q

Smooth Muscle Relaxation

• Ca2+ must be ____ to stop contraction.
• Two major ways:
– Sarcoplasmic reticulum: ____ pumps Ca2+ back into the SR.
– Sarcolemma: ____ and ____ export Ca2+ back to the extracellular space.
• Major routes of Ca2+ entry and exit from SM cytoplasm:
– Left: ↑[Ca2+] → contraction.
– Right: ↓[Ca2+] → relaxation.

Modulators that induce relaxation from even the tonic state > mediate exit of calcium > most of calcium will be exported back to the ____ > Na/Ca channels, sarcolemma located Ca ATPase, or a smooth muscle SERCA at membrane of SR > some of calcium stored back into the SR

A

removed
Ca++-ATPase
Na+/Ca++ exchanger
Ca++-ATPase

extracellular space

26
Q

SM Contraction Summary

Contraction

  1. Ca2+ imported (mostly) from ____ and (less) from ____.
  2. Ca2+ binds ____.
  3. Ca2+-calmodulin activates ____.
  4. MLCK phosphorylates ____.
  5. Phosphorylated (active) myosin ____ and binds actin filaments: start of the ATP- dependent contraction cycle (cross-bridge).
  6. Contraction continues as long as myosin remains ____.
A
EC fluid
SR
calmodulin
MLCK
myosin light chain regulatory regions
unfolds
phosphorylated
27
Q

Smooth Muscle Relaxation Summary

Relaxation

  1. Ca2+ levels are reduced by pumping back to the SR and extracellular fluid.
  2. Ca2+ liberates from ____, which inactivates ____.
  3. Myosin-light chain phosphatase (MLCP) dephosphorylates ____.
  4. Inactivation of myosin ATPase stops the cross-bridge cycle.
A

calmodulin
MLCK
regulatory myosin light chains

28
Q

Neural Control: G-protein coupled receptor pathway

  • GPCR-mediated contraction:
  • Muscarinic acetyl choline receptor (mAChR, typically ____):
  • Typical of ____ muscle.
  • Binding of ____).
  • α1 adrenergic receptor (α1R):
  • ____.
  • Binding of ____ (epinephrine and norepinephrine).

• Both: Activation of ____ → production of ____ and ____

  • Mechanisms of contraction:
  • Release of Ca2+ from the ____.
  • Inhibition of K+ channels, preventing hyperpolarization of the sarcolemma.

These receptors will activate the GPCR > activates a series of phospholipase (C ) > production of IP3 > binds to a receptor in the SR, which is a ____ calcium channel > exports calcium from internal stores > induces contraction

No measure of AP > dependent totally on ligands, no ____

A

M3
GI smooth
ACh

BV
catecholamines

phospholipases
IP3
DAG
SR

receptor
electrical activity

29
Q

Neural Control: cAMP pathway

  • β-adrenergic relaxation:
  • ____ smooth muscles:
  • Adjustment of ____ and ____.
  • Response to ____ (epinephrine and norepinephrine).
  • Activation of ____ and formation of cAMP.
  • cAMP can be inactivated to AMP by a ____.
  • Mechanisms of relaxation:
  • ____ phosphorylation (inactivation) of MLCK.
  • Stimulation of Ca2+ reuptake by the SR (not shown).

Dropping blood pressure, increasing blood flow [???]

A

vascular
blood flow
pressure
catecholamines

adenylyl cyclase
phosphodiesterase (PDE)

cAMP-dependent protein kinase (PKA)

30
Q

Neural Control: cAMP Pathway

Epi and norepinephrine binds B2 > formation of cAMP from adenylate cyclase activation > PKA > phospho MLCK > inactive

Even if calcium is present, the activity of MLCK will be lower > cannot bind to the complex > cannot induce phospho of myosin > INDEPENDENT OF THE ____ > relaxation of SMC

A

calcium concentration

31
Q

NE released by sympathetic system > acts on SMC located in BV in the GI/stomach > ____ > activates GPCR pathway > contraction (vasoconstriction); however, in lung, NE binds ____ > relaxation

In gut/stomach, ACh binds ____ > peristalsis; in lung, ACh binds ____ > constriction

Depending on the ____ of the SMC > the end effect of the cell is completely opposite/different (completely different pathways)

A

A1R
B2

MAchR
MAchR

receptor

32
Q

Neural Control: NO pathway
• Nitric Oxide (NO) relaxation:
• ____ smooth muscles:
• Adjustment of ____ and ____.
• Response to NO produced by ____ cells.
• Activation of ____ which produces cGMP.
• cGMP can be inactivated to GMP by a ____.

  • Mechanisms of relaxation:
  • cGMP-dependent protein kinase (PKG) activation of ____.
  • Prevents entry and promotes reuptake Ca2+.
  • Opens K+ channels that hyperpolarize the sarcolemma.

NO produced by NO synthase > guanylate cyclase > cGMP > PKG > acts on ____ > activates it > converts active myosin into inactive > relaxation

A
small artery
blood flow
pressure
guanylyl cyclase
phosphodiesterase (PDE)

MLC phosphatase

MLC phosphatase

33
Q

Smooth Muscle Contractile Activity Patterns

• Essential difference with skeletal muscle: Smooth muscle can ____ or ____ in response to a stimulus.

  • Tonic smooth muscles:
  • Continuously ____: normally contracted.
  • ____ steady-state force.
  • ____, blood vessels, and airways.

• Phasic smooth muscles:
• ____ contractions:
• Walls of the ____ and urogenital
tracts.

• Normally relaxed smooth muscles:
• May contract intermittently during physiological
activities under ____ control:
• Voiding of ____ and swallowing.

In sphincters, induced to relax completely or contracted

GI/stomach > phasic activity > contraction or relaxation > induce persistalsis

SMC in the esophagus, usually relaxed, but contract when we voluntarily swallow something

A
contract
relax
active
variable
sphincters

rhythmic
GI

voluntary
urine

34
Q

Smooth Muscle Mechanical Properties

  • From ____ measurements: Length-tension relationship:
  • Similar to skeletal muscle: mainly due to the degree of ____ of thin and thick filaments.
  • One difference: SM has more connective tissue and thus has more ____.
  • SM operates over a ____ of resting lengths than striated muscles.
A

isometric
overlapping
passive force
wider range

35
Q

Smooth Muscle Mechanical Properties

From ____ measurements: Force-velocity relationship:

Similar in overall ____ in smooth and skeletal muscles:
– Depends on load.
– ____ at zero load.

  • Differences:
  • Lower ____ of contraction: due to lower ATPase activity of SM myosin.

Inverse relationship graph similar to what was seen last week

A

isotonic
shape
maximal

velocity

36
Q

Smooth Muscle Mechanical Properties
• Differences:
• Lower velocity of contraction: due to lower ATPase activity of SM myosin.
• ATPase activity depends on ____: changes in degree of phosphorylation will affect ____ as well as ____ generated.

Filament can contain phos and non-phos myosin heads; degree of phos it can be very high or very low

If most myosin molecules are phospho > 60%: greatest curve; if only 10% > lowest curve; ____ of containing 10% is much lower, because only phos molecules are active

Not phospho > the ____ (x-axis) generated from the SMC is very low

A

phosphorylation
velocity
maximal stress

velocity
force

37
Q

Smooth Muscle Adaptation

  • Hormone-induced hypertrophy:
  • Typical of ____.
  • ____induced on SM-rich uterine myometrium (up to 70-fold).
  • Increase in ____ and ____.
  • Other forms of hypertrophy:
  • Blood vessels: due to ____.
  • Urinary bladder, small intestine: due to ____.
  • Phenotypic transformation:
  • Switch from contractile to synthesizing phenotype (of collagen, elastin, LDLs).
  • Typical of ____ and ____.

Conversion of contractile to synthesizing > change ____ pattern > remove contractile mechanisms, and only produce substances (ECM proteins) > fibrosis (pathological response to ____ or invasion of ____)

A

pregnancy
progesterone and estrogen
muscle size (hypertrophy)
cell number (hyperplasia)

chronic hypertension
chronic obstruction

fibroses
artherosclerosis

gene expression
chronic inflammation
toxin

38
Q

Skeletal vs. Smooth Muscles

Skeletal Muscle:

Made of \_\_\_\_ myofibers.
Striated myofibers are large and \_\_\_\_:
average length = \_\_\_\_
average diameter = \_\_\_\_
No \_\_\_\_ among cells.
\_\_\_\_ types of myosin (fast and slow) and \_\_\_\_ types of muscles (fast and slow)
Glycolytic and oxidative metabolism (relatively inefficient).
\_\_\_\_.
Upon stimulation, muscles can only \_\_\_\_.

Smooth Muscle:
Smooth muscle cells (no ____). Cells are small and ____:
average length = ____
average diameter = ____
Cells are connected ____ via desmosomes and ____ via gap junctions.
____ type of myosin (slow myosin produced by the Slow Myosin gene).
Energy from oxidative metabolism (____ times more efficient than skeletal muscle).
____.
Exhibit ____ (i.e. prolonged contraction with minimal use of energy).
Upon stimulation, SMs can either ____ or ____.

A
striated
multinucleated
cm
100-200 um
connections
two
two
voluntary
contract
cross-striations
single-nucleated
50-500 um
2-10 um
mechanically
functionallysingle
10-300x
involuntary
tone
contract
relax