Muscles Flashcards
Cyclically binds with myosin cross-bridges during contraction
Actin
Possesses ATPase actvity
Myosin
Supplies energy to the myosin cross-bridge, moving it into “cocked” position
ATP
Transmits action potentials to the interior of the muscle fiber
T-tubule
Stores Ca2+ within the muscle fiber
Sarcoplasmic Reticulum
Binds to troponin, causing tropomyosin to shift out of its blocking position
Ca2+
Prevents myosin heads from binding to actin when the muscle fiber is at rest
tropomyosin
Required for detachment of the myosin heads from the actin filament
ATP
Almost all cells have ___.
intracellular machinery for movement
What are the contraction specialists of the body?
Muscle Cells
What are the 3 types of muscle cells?
Smooth
Skeletal
Cardiac
What is the basic function of muscle cells?
`Highly developed ability to contract, develop tension and do work
What does contraction of muscle allow?
- Purposeful movement of the body in relation to the environment
- Manipulation of external objects
- Propulsion of contents through hollow organs
- Empty the contents of organs to the environment
What is meant by contraction of muscle allows “purposeful movement of the body in relation to the environment”?
Skeletal muscle moves bone to allow movement
What is meant by contraction of muscle allows “manipulation of external objects”?
it allows you to peel fruit, move furniture, etc.
What is meant by contraction of muscle allows “propulsion of contents through hollow organs”?
contraction of smooth and cardiac muscle allows contents to move through the body
ex: blood pumping through heart (cardiac muscle), intestines (smooth muscle)
What is an example of “propulsion of contents through hollow organs” in cardiac muscle?
the heart pumping blood
What is an example of “propulsion of contents through hollow organs” in smooth muscle?
intestines
What is meant by contraction of muscle allows “empty the contents of organs to the environment”?
it allows our bodies to empty things like our bladder and uterus
contraction of smooth muscle allows us to empty our bladder
What comprises the largest group of tissues in the body?
muscle
How is muscle classified?
based on appearance (striated or unstriated)
based on function (voluntary (somatic) and involuntary (autonomic))
How is Skeletal Muscle classified?
striated (orderly)
voluntary (somatic)
How is Cardiac Muscle classified?
Striated (orderly)
Involuntary (Autonomic)
How is Smooth Muscle classified?
Unstriated (unorganized)
Involuntary (autonomic)
What does the afferent division of the PNS do?
it brings stimuli from outside world to the CNS and about the state of affairs in your body (all sensory info, if you’re in pain, your temp, digestion, etc.)
Awareness (shoutout Kaylea)
What is the efferent division of the PNS?
effect us and our environment
made up of Somatic Nervous System (gives us control over skeletal muscle)
and Autonomic Nervous System (consists of flight or flight (sympathetic) and rest and digest (parasympathetic))
What does the Somatic Nervous System do?
motor neurons that control skeletal muscles
What does the Autonomic Nervous System do?
Sympathetic and Parasympathetic nervous systems that control smooth and cardiac muscles and glands
What is the Peripheral Nervous System (PNS)?
PNS consists of fibers that bring information back and forth between the CNS and outside world
What are the levels of organization in skeletal muscle?
whole muscle = organ
muscle fiber = a cell
myofibril = intracellular structure
thick and thin filaments = myofilaments
myosin and actin = contractile proteins
What is a muscle fiber?
a very large, multinucleated muscle cell
made up of myofibrils
Why are muscle fibers multinucleated?
to maintain high protein production of such a large cell
What makes up the sarcomere?
myofilaments
How are tendons formed?
from muscle fibers that have alot of connective tissue
What are the thick filaments in a muscle cell?
myosin
What is myosin made up of?
two myosin subunits and a head (cross-bridge)
What do Light Chains do?
They enhance myosin-actin interactions
What are thin filaments in a muscle cell?
actin
How does actin form a chain?
it polymerizes
What is Globular (G) actin?
actin that is a free floating monomer and hasn’t formed a chain yet
What is tropomyosin?
A long regulatory protein that lays where myosin wants to bind on actin
What is troponin?
A regulatory protein that attaches to tropomyosin and helps it to stabilize and move allowing myosin to bind to actin
it has three subunits
What is the Sliding Filament Theory of Muscle Contraction?
Thick and thin filaments slide past each other to cause contraction
What does shortening do to banding in muscle cells?
It causes it to change
What is the A band?
all thick filament and any thin filament that overlaps it
What happens to the A band as the muscle contracts and relaxes?
it stays the same width because the thin filaments just slide by it
What is the I band?
The remaining portion of the thin filaments that do not project into the A band
What happens to the I band as the muscle contracts and relaxes?
It gets shorter as the muscle contracts because of thick and thin bands sliding
What is the Z line?
In the middle of the I band
where thin filaments attach
What is the H zone?
The lighter area in the middle of the A band, where thin filaments do not reach
thick filament with no thin filament overlapping
What is the M line?
The mid point of the Sarcomere
What is the sarcomere?
Z line to Z line
What does the M line do?
It keeps thick filaments in correct structural orientation
What is the Dark band?
The A band
What is the Light band?
the I band
What is the order of the bands from Z line working inward?
Z, I, A, H, M
Zee Intelligent Animal Has Muscle
Which of the following remains the same width during contraction?
A band
H zone
I band
A band
Which of the following describes a sarcomere?
A. 1 whole A band and ½ of each I band located on either side
B. 1 Z line to the next Z line
C. The functional unit of skeletal muscle
D. All of the above
All of the above
What occurs in the muscle during resting state?
Troponin and Tropomyosin are blocking the myosin binding site on actin
The myosin cross-bridge is held back
No attachment is possible between actin and myosin filaments
muscle is relaxed
What is Excitation-Contraction Coupling?
Excite the muscle when you want it to contract
During the resting state of a muscle, what is absent from the sarcoplasm?
Ca2+
What does the SERCA do?
It actively pumps Ca2+ into the SR
What are the steps in excitation of the muscle?
- membrane is depolarized
- when action potential reaches the nerve terminal, the depolarization opens voltage-gated calcium channels
- when calcium channels open, Ca2+ rushes in
- Influx of Ca2+ signals vesicles with ACh to fuse with active zones
- active zones release their content
- ACh diffuse across the neural muscular junction
- After diffusing across the neural muscular junction, ACh will bind to either:
- Acetylecholine binding site
- Acetylcholinesterase site
What happens during muscle excitation when the membrane action potential reaches the nerve terminal?
the depolarization opens voltage-gated calcium channels
What happens during muscle excitation when the voltage-gated calcium channels open?
Ca2+ rushes in
What does an influx of Ca2+ cause during muscle excitation?
influx of Ca2+ signals vesicles with ACh to fuse with active zones
During muscle excitation, what happens to active zones when ACh fuses with them?
they release their content and ACh diffuses across the neural muscular junction
During muscle excitation, what happens to ACh after it diffuses across the neural muscular junction?
it can either bind to the acetylcholine binding site or the acetylcholinesterase site
During Muscle excitation, what happens to ACh if it binds to the acetylcholine binding site?
It opens a cation channel allowing Na+ in and K+ out and causes depolarization (End Plate Potential (EPP)), which causes the muscle to contract
What kind of receptor is the acetylcholine binding site?
a nicotinic cholinergic receptor
What is the end plate potential (EPP)?
It is a depolarization event during muscle excitation that spreads along the muscle and causes an action potential, resulting in muscle contraction
During muscle excitation, what happens if ACh binds the acetylcholinesterase site?
The acetylcholinesterase site degrades ACh and ends the signal for muscle contraction
What is the sarcoplasmic reticulum (SR)?
modified ER, consisting of interconnecting tubules surrounding each myofibril like a mesh sleeve
a specialized membrane that takes AP from surface to center of cell
Where Calcium is stored
Where is calcium stored in the muscle?
Sarcoplasmic Reticulum
What is the T-Tubule?
it brings depolarization perpendicular to the surface of the muscle
a specialized membrane that take s AP from surface to the center of the cell
What does the spread of the action potential down T-tubules cause?
It activates Dihydropyridine receptors (DHPR)
What does a Dihydropyridine receptor (DHPR) do?
it is a voltage-gated calcium channel that prevents Ca2+ from coming in, functioning as a voltage sensor in skeletal muscle and triggering intracellular release of Ca2+ via the Ryanodine receptor (RyR)
shifts with voltage change
Where does the Dihydropyridine receptor (DHPR) function? What does it do?
In skeletal muscle as a voltage sensor to trigger release of Ca2+ from RyR
What does the Ryanodine receptor (RyR) do?
It allows Ca2+ to enter the cell when activated by the DHPR
What kind of channels are DHPRs and RYRs?
Ca2+ receptors
What is the steric block model of muscle contraction?
At rest, Tropomyosin and Troponin are preventing myosin from binding to actin
During exercise, an influx of intracellular Ca2+ binds to the C subunit on troponin.
This causes troponin to roll, moving tropomyosin in the process and uncovering actin’s binding site
This allows myosin to bind
What are the three subunits of troponin and what do they do?
T subunit (binds tropomyosin)
C subunit (binds calcium) I subunit (inhibits)
What must happen before myosin cross-bridges link to actin?
ATP is hydrolyzed by myosin ATPase
ADP and P remain attached to myosin
Energy stored in cross-bridge
What is Cross-bridge cycling?
- cross-bridge (myosin head) is energized
- Ca2+ removes inhibitory influence (troponin-tropomyosin complex)
- Energized myosin binds actin, contact of myosin on actin “pulls the trigger” and causes a power stroke, ADP and P are released
- Binding of fresh ATP breaks the linkage between actin and myosin (decreases affinity for actin), and ATP is hydrolyzed (changing myosin head conformation)
What is the “power stroke” during myosin cross-bridge cycling?
M1 binds to actin, bringing M2 closer and allowing it to bind as well
M2 binds and allows M3 to bind
M3 binds and allows M4 to bind
M4 has the highest affinity for actin
What happens to cross-bridge cycling if no fresh ATP comes in (like after death)?
Contraction occurs but no fresh ATP is around to cause detachment of myosin from actin causing rigor mortis
What is responsible for removing the steric inhibition for the act of contraction?
Ca2+
What is responsible for detachment?
ATP
How does a muscle return to resting state?
- neural excitation stops (no more depolarization down the membrane or across the T tubule)
- previously released ACh is broken down by AChase
- Muscle excitation stops
- Dihydropyridine channels close; diffusion of Ca2+ out of SR stops
- SERCA pumps Ca2+ back (decrease in intracellular Ca2+)
- Actin’s binding sites are covered; actin slides back into relaxed position away from center of sarcomere
All of the following result in muscle relaxation EXCEPT:
A. Reuptake of Ca2+ by the SR
B. No more ATP
C. No more AP
D. Removal of ACh at the end plate by AChase
E. Filaments sliding back to their resting position
No more ATP
How does black widow spider venom affect the NMJ?
it alters the release of ACh
toxin can form pores in presynaptic membrane causing an explosive release of ACh from synaptic vesicles, which can result in respiratory failure
causes muscle contraction but no relaxation
How does clostridium botulinum toxin affect the NMJ?
it alters the release of ACh
it blocks the release of ACh and prevents contraction, causing respiratory failure
What is Clostridium botulinum toxin used for?
Botox to treat chronic back pain due to muscle spams
What does Curare do to the NMJ?
it blocks ACh receptors
it reversibly binds to ACh receptor, blocking it and preventing muscle contraction
it can causes muscle paralysis by causing relaxation and can result in respiratory failure
What are derivatives of Curare used for?
to relax skeletal muscles during surgery
How does Myasthenia Gravis affect the NMJ?
it blocks ACH receptors
antibodies inactivate ACH receptor
it inhibits the enzyme that breaks down ACh, causing more ACh to be available that bounces around until it finds a receptor
What does the drug neostigmine do and what is it associated with?
Myasthenia Gravis
it is a short-term anti AChase to break down excess ACh
it increases the likelihood a contraction can still happen
What do organophosphates do to the NMJ?
Prevents inactivation of ACh
it irreversibly inhibits AChase, preventing relaxation
the diaphragm is unable to repolarize and it can cause respiratory failure
What agents affect the NMJ by altering the release of ACh?
Black widow spider venom
Clostridium botulinum toxin
What agents/diseases affect the NMJ by blocking the ACh receptor?
Curare
Myasthenia Gravis
What agents/diseases affect the NMJ by preventing inactivation of ACh?
organophosphates (certain pesticides and nerve gases)
What agents/diseases that affect the NMJ can result in respiratory failure?
Black widow spider venom
Clostridium botulinum toxin
Curare
Organophosphates
What are the similarities between the synapse vs. NMJ?
Both have…
- 2 excitable cells separated by a narrow cleft that prevents direct transmission of electrical activity (can’t get from one neuron to another or the muscle directly)
- Axon terminals store NT that are released by Ca2+-induced exocytosis of storage vesicles
- Binding of NT with receptor opens membrane channels, permitting iconic movements that ΔMP
- Resultant Δ in MP is graded potential
What is a graded potential?
a short term depolarization or hyperpolarization or short distance signals
What are the differences between Synapses and NMJs?
Synapse: A junction between 2 neurons; Excitatory (EPSP) or inhibitory (IPSP)
NMJ: Exists between a motor neuron and a skeletal muscle fiber; Always Excitatory (EPP)
What are the three energy systems in skeletal muscle?
Oxidative
Non oxidative
Intermediate
What is the immediate energy system of skeletal muscle?
energy is immediately available to support muscle contraction
consists of a single enzyme pathway
used up fast
readily available but not long lasting
What are some examples of immediate energy systems?
ATPase: ATP + H2O → ADP + Pi
CK: CP + ADP → ATP + Cr (CP has high energy phosphate, found in brain, heart, and skeletal muscle)
Myokinase: ADP + ADP → ATP + AMP (recycling pathway)
How many times greater is the amount of CP in resting muscle than ATP?
CP is 5-6x greater than ATP in resting muscle
What is the nonoxidative energy system in skeletal muscle?
Energy sources in muscle = breakdown of glucose and glycogen
Ideal for the first minute of exercise then starts to decrease
breaksdown glucose or glycogen through Glycogenolysis and Glycolysis
No O2
less efficient than oxidative
generates lactic acid (decreases muscle pH)
____ and ___ energy sources combined provided a fraction of the energy that ___ metabolism can
- immediate
- nonoxidative
- oxidative
What is the oxidative energy system?
uses energy sources for muscle: carbohydrates (glucose and glycogen), fats, and certain amino acids
slow to activate
Oxidative Phosphorylation: Slow, requires O2, highly efficient
goes through Krebs Cycle and ETC
How much ATP is made in Glycolysis and the Oxidative energy system?
Glycolysis: glucose → 2ATP
Oxidative: glucose → 36 ATP
Oxidative: palmitate → 129 ATP
What is the purpose of immediate and Non-oxidative pathways?
They give the initial burst of energy to hold the body over until the oxidative system activates
Immediate and Nonoxidative: activated rapidly; produce energy at a high rate
Oxidative: slow to activate: produce energy at a low rate
How are skeletal muscle fibers categorized?
Based on:
Speed of contraction (myosin ATPase activity) (what isoform of myosin ATPase is in the muscle)
Type of metabolic pathway → ATP (oxidative or glycolytic)
Type 1 Muscle Fibers
Slow Twitch
red in color → high mitochondria and myoglobin content
Oxidative Capacity: high
Glycolytic Capacity: low
Contractile Speed: slow (often activated)
Fatigue Resistance: high (not prone to fatigue)
Motor Unit Strength: low (not used when you need a lot of muscle power)
Type IIa muscle fibers
Fast-twitch a
high mitochondria content → red color
Oxidative Capacity: Moderately high
Glycolytic Capacity: High
Contractile Speed: Fast
Fatigue Resistance: Moderate
Motor Unit Strength: High
Type IIx (Type IIB) muscle fibers
Fast-twitch
low mitochondria and myoglobin content: white fibers
Oxidative Capacity: Low
Glycolytic Capacity: Highest
Contractile Speed: Fast
Fatigue Resistance: Low (fatigues easily)
Motor Unit Strength: (gives a lot of power)
What types of exercise use Type I Fibers?
Low-intensity aerobic exercise, daily activities
What types of exercise use Type IIa fibers?
more force, faster fatigue than type I
short, high-intensity endurance events (1,600 m run)
What types of exercise use Type IIx fibers?
Seldom used for everyday activities
Short, explosive sprints (100m)
What fiber type predominates in endurance athletes?
Type I
What fiber type predominates in power athletes?
type II predominates
what determines the kind of fibers that will predominate in a person?
genetics
training
aging
How do genetics effect fiber type?
determine which α-motor neurons innervate fibers
fibers differentiate based on α-motor neuron
How does training effect fiber type?
muscle fiber type is influenced little by training
it is possible to transition from FOG ←→ FG
Endurance training can increase oxidative capacity of all 3 fiber types
How does aging effect fiber type?
muscles lose type II motor units over time
What is a motor unit?
Motor unit = 1 motor neuron + all the muscle fibers it innervates (activates)
What happens when a motor neuron is activated?
When a motor neuron is activated, all of the fibers it supplies are stimulated to contract simultaneously
How do you obtain stronger contractions?
recruit more motor units
How does your muscle produce less force?
activate just a few fibers
smaller motor units (type I)
creates precise, delicate movements
What is an example of less force production in muscles?
Hand: one motor unit may contain a dozen muscle fibers
How does your muscle produce more force?
activate alot of fibers
larger motor units (type II)
Powerful, course movements
gives large increments of power
What is an example of more force production?
Legs: one motor unit contains 1,500 to 2,000 muscle fibers
How does the CNS increase muscle force?
by activating additional motor units in the order of their increasing size, beginning with the smallest
recruit more motor units for more force
What is the recruitment order of muscle fibers for increasing force?
Type I, type IIa, type IIx
What must take place before changes in muscle size?
Neural Adaptations
What causes early gains in strength training?
neural factors (which optimize recruitment patterns)
we get better at recruiting motor neurons
What happens later on in strength training?
increasing cross-sectional area (hypertrophy) becomes more important
What is muscle tone?
small amount of tension due to weak, involuntary contractions of its muscle fibers
low level of contraction
When is muscle tone exhibited?
at rest
What is the purpose of tone?
it keeps muscles primed and ready for action
skeletal muscles are kept firm, without producing movement
How is muscle tone sustained?
motor unit groups alternately contract and relax
Why is muscle tone important?
important in maintaining posture (e.g. sitting)
The force exerted by the same muscle can vary depending on:
what you pick up (piece of paper, book, 50 lb. weight)
What are the two major factors that determine gradation of whole muscle tension?
- The # of muscle fibers contracting within a muscle (# of motor units recruited, size of the motor unit)
- The tension developed by each contracting fiber (frequency of stimulation, length-tension relationship)
How does frequency of stimulation effect the tension developed by each contracting fiber?
repetitive stimulation → contractions of longer duration and greater tension
What happens to muscle tension with a single twitch?
The fiber is completely relaxed before the next Action Potential
can’t do much work
one muscle contraction
What happens to muscle tension during a twitch summation?
the fiber is stimulated a 2nd time before it has relaxed → greater tension
calcium accumulates intracellularly and enables more work to be done
Why is twitch summation possible?
because the action potential is 1-2 msec
What happens to muscle tension during tetanus?
fiber is stimulated so rapidly → no relaxation
smooth sustained contraction
What is the length-tension relationship?
The relationship between initial length and tension can be explained by the # of cross-bridges that can be formed during contraction
What can affect the extent of fatigue in a muscle?
Duration of activity
Amount of asynchronous recruitment of motor units
Type of fiber (fatigue-resistant/fatigue-prone)
What affects the thickness of a fiber?
type of fiber (small diameter oxidative vs. large diameter glycolytic)
pattern of neural activity (hypertrophy vs. atrophy)
Amount of testosterone
What are the two types of muscle contraction?
Isometric (same length)
Isotonic (same tension)
What is isometric muscle contraction?
Muscle produces force but does not change length
joint angle does not change
myosin cross-bridges form and recycle, no sliding; static (wall sit, plank)
What is isotonic muscle contraction?
Muscle produces force and changes length
joint movement produced; dynamic (picking up a phone)
What are the isotonic contraction subtypes?
Concentric contraction
Eccentric contraction
What is Concentric contraction?
muscle shortens while producing force
most familiar type of concentration
sarcomere shortens
What is Eccentric Contraction?
Muscle lengthens while producing force
cross-bridges form but sarcomere lengthens
EX: lowering heavy weights, running down hill
What is Sarcopenia?
Loss/atrophy of muscle with advancing age
starting in our late 30’s to early 40’s, most people lose ¼ lb of muscle every year
___ is the absolute centerpiece for being healthy, vital, and independent
Muscle
What happens if strength and power decrease?
risk of falling and fractures
affects daily activities
What happens as Basal Metabolic Rate (BMR) decreases?
Impaired thermoregulation (lose metabolic reactive tissue)
slower recovery from injury and damage
What happens as Body Fat increases?
insulin sensitivity decreases
insulin resistance increases
can cause prediabetes
What happens if Bone Density decreases?
risk of osteoporosis
What happens if Physical Activity and VO2 max (indicator of aerobic activity) decrease?
Fatiguability
loss of mobility
loss of independence - reduced quality of life
What can cause muscle growth?
Hormones
Exercise
Protein
What can cause muscle loss?
Malnutrition
Inactivity
Illness/injury
What hormonal milieu changes occur with age?
Muscle growth (synthesis) decreases with age)
Synthesis hormones (GH, IGF-I, T) decrease with age preventing muscle growth
Stress hormone (cortisol, cortisol cytokines) increase with age and inhibit synthesis
IGF-I and Insulin inhibit breakdown of muscle but both decrease with age
Muscle degradation increases with age
What happens to catabolic and anabolic signals as we age?
Catabolic signals increase with age (degradation)
Anabolic signals decrease with age (synthesis)
What happens to muscle fiber with age?
it decreases
What happens to muscle fiber area atrophy with age?
it decreases
What happens to motor units in EDL with age?
it decreases
What happens to injury response in muscles as we age?
Muscles from old animals are more susceptible to injury
injury may play a role in dev’p of muscle atrophy and weakness that occurs with aging
we tend not to repair muscle after injury with age
What can injury cause in muscles in old age?
muscles in old animals display prolonged, possibly irreversible, structural and functional deficits
Summary of age-related changes
with age, connective tissue increases and muscle fibers decrease
muscles become stringier and more sinewy
by age 80%, 50% of muscle mass is lost (sarcopenia)
decreased density of capillaries in muscle
reduced stamina
increased recovery time
regular exercise reverses sarcopenia
decrease protein synthesis
What can we do to prevent muscle loss?
strength train (protects young and old muscles from injury and can present sarcopenia)
eat enough protein (spread protein throughout the day)
What is the most powerful aa stimulating protein synthesis?
Leucine
What are high leucine foods?
cheese, soybeans, seaweed, beef, chicken, pork, nuts, seeds, fish, seafood, and beans
Where is smooth muscle located?
walls of hollow organs (gallbladder, uterus, bladder)
Tubes (GI tract, blood vessels)
What does all smooth muscle exhibit and why?
all smooth muscle exhibits tone (basal tension); contractions superimposed on tone
it maintains shape and pushes contents along
How does smooth muscle contract?
- slow to contract and relax
- slower and longer contraction vs. sk muscle
- generates comparable force using 300 times less ATP
- gives up speed for ability to adapt and adjust
- responds to variety of stimuli: nerves, hormones, stretch, etc.
- Latch state possible: prolonged contraction w/o input ATP
What are the diverse functions of smooth muscle
See chart
What does smooth muscle lack compared to skeletal muscle fibers?
Sarcomeres
Troponin
T-tubules
What does smooth muscle have compared to skeletal muscles?
- Dense bodies (take place of Z line) anchors actin; held in place by intermediate filaments
- Tropomyosin, but role unclear
- Caveolae: indentations in sarcolemma
- may act like T tubules
- SR, but not well developed
- not alot of calcium
What happens to smooth muscle during contraction?
smooth muscle gets smaller in length and wider
What is the arrangement of actin/myosin in smooth muscle?
- Oriented diagonally
- diamond-shaped lattice (not parallel with long axis)
- sliding causes cell to shorten and expand
- long thin filaments allow a large range of shortening (to fully expel bladder)
What are the two types of smooth muscle?
Single Unit
Multi Unit
What is single unit smooth muscle?
smooth muscle gets excited and contracts as a single unit
cells are connected by gap junctions and only need to stimulate one or two in order to spread the message to all cells and contract as one
Describe the electrical activity in smooth muscle cells.
Spontaneous electrical activity initiated by pacemaker cells (spread throughout the muscle)
2 types (slow wave potentials and action (spike) potentials
How do slow waves coordinate muscle contractions in the gut?
by controlling the appearance of a second type of depolarization event - Action Potentials only occur at the crests of slow waves
What is the Resting Membrane Potential (RMP) in excitation-contraction coupling?
- It is relatively low (-50 to -60 mV)
- 30 mV above K+ equilibrium
- Higher Na+ permeability
- 1 Na+: 100 K+ in skeletal muscle
- 1 Na+: 5 K+ in smooth muscle
What is the AP in excitation-contraction coupling in smooth muscle?
- Long AP = 10-50 ms (vs 2-3 ms in sk muscle)
- No voltage-gated Na+ channels at “motor end plate”
- voltage gated Ca2+ channels (dihydropyridine)
What are the 3 Dihydropyridine Receptors?
Skeletal: voltage sensor (not functional Ca2+ channel)
Cardiac: voltage-dependent Ca2+ channel; only lets in a little Ca2+ (triggers release of other Ca2+)
Smooth: voltage-dependent Ca2+ channel; lets in enough Ca2+ for AP
What is the role of Ca2+ in contraction in smooth muscles?
Role of Ca2+: the state of the thick filaments (not thin) are affected by Ca2+
Where does Ca2+ come from in smooth muscles?
- Most from outside the cell
- depolarization → voltage-gated Ca2+ channels open
- NTs, hormones etc. open Ca2+ channels
- A little Ca2+ is released by the SR
What is the mechanism for smooth muscle contraction?
- Extracellular Ca2+ enters via:
- voltage-gated channels (aka L-type, aka DHPR)
- ligand-gated channels (responds to nerves, hormones, stretch)
- stretch-activated channel (responds to nerves, hormones, stretch) (happens in blood vessels)
- Chemical Activation:
- Ca2+ binds to calmodulin, leading to activation of myosin light chain kinase (MLCK).
- MLCK phosphorylates the light chain of myosin.
- When myosin is phosphorylated (binds to actin), cross-bridges can form and break repeatedly
What is the difference between myosin in smooth muscle and skeletal muscle?
Smooth: myosin is “off”
Skeletal: myosin is always “on”
What is the smooth muscle relaxation mechanism?
- Relaxation is a result of:
- removal of the contractile stimulus (decreased [Ca2+])
- Direct action of a substance that inhibits the contractile mechanism (increased myosin phosphatase activity
How can vascular smooth muscle (aorta) endure 60 “insults” per minute and sustain BP w/o expending a lot of ATP?
- Develop force
- Smooth muscle has a way for cross bridges to remain attached, cycle slowly and consume less ATP
What is the mechanism of tonic concentration?
- Dephosphorylation of myosin while it is still attached to actin
- dephosphorylated → ATPase activity decreases
- more difficult to release myosin heads from actin; slow cross-bridge cycling (low ATP use)
- dephosphorylated → ATPase activity decreases
Summary of Smooth Muscle
- involuntary, non-striated muscle associated with blood vessels and visceral organs
- overlapping myofilaments
- sliding filaments generate force
- increased intracellular Ca2+ regulates myosin
- Ca2+ increased through
- mechanically gated Ca2+ channels
- Ligand gated Ca2+ channels (ANS, hormones, paracrine)
- Voltage gated Ca2+ channels
- Capable of phasic contraction and tonic contraction
