NMJ MUSCLE ALL Flashcards
Sequence of events from AP in a Motorneuron to AP in Sarcolemma of Muscle Cell
- AP travels along motoneuron axon
- AP invades motoneuron presynaptic terminal
- Ca 2+ influx in presynaptic terminal
- Vesicle fusion (exocytosis) with membrane of presynaptic terminal
- Release of Ach from fused vesicles
- Diffusion of ACh across neuromuscular cleft
- Binding of Ach to its receptors (AChR) in postsynaptic membrane (motor end plate)
- Opening of Na+ and K+ channels which are chemically regulated
- Na Influx and small K+ efflux across motor end plate
- generation of endplate potential
- opening of voltage-gated Na channels in sarcolemma immediately surroudning the motor endplate
- AP in sarcolemma
what is the site of regulation of skeletal muscle by the nervous system
NMJ
how many NMJ are found on most skeletal muscle cells
One NMJ on the surface membrane (sarcolemma)
how much space does the NMJ take up on the sarcolemma
less than .1%
specialization of the NMJ membrane
Highly specialized membranes (motor neuron and muscle)
the membrane of a muscle
Sarcolemma
where the neuron meets a muscle
Motor end plate
location of AChRs, and sodium channels in the post-synaptic membrane
ACHR’s are close to the motor nerve at the top of the secondary folds
Na Channels are at the bottom of the secondary folds
where is Acetylcholinesterase in the motor end plate
at the basin of the secondary folds near Na Channels
who has more complex motor end plates, adults are children
Adults
Comparison of the Neuromuscular cleft size to a vesicle at the NMJ
vesicle is 200 Angstrum
Cleft is 400 Angstrum
what causes a change in membrane potential at the motor endplate
ACh binding to its receptor following AP in motoneuron terminal
are changes in the endplate potential spontaneous
No
Are Endplate potential changes an all or none response
No, they are graded
Propogation of Endplate Potential
Do not propagate, contined to the end-plate region
Amplitude of Endplate Potential
about 10 mV (AP is 130 mV)
does changes in endplate POtential lead to AP
can undergo summation, but usually lead to an AP
what are miniature Endplate Potentials
Small endplate potentials
when do Miniature Endplate Potentials occure
spontaneously at rest
why do Miniature Endplate Potentials occur
Result from release of ACh from one vesicle
where do Mini endplate potentials occure
Confined to end-plate region
Amps of the Miniature Endplate Potentials
1-2mVc
Can Mini endplate Potentails do summation
Yes by the release of a few vesicles at the same time or in close proximity (both temporal and spatial)
what breaks do ACh
Acetylcholinesterase
location of Acetylcholinesterase
on the motor endplate membrane in the basal lamina
what results from the breakdown of ACh
Acetic acid (acetate) and Choline
what happens to the Acetic acid and Choline from the breakdown of ACh
Acetate= circulation Choline= presynaptic terminal, then reacts with acetyl-Coa by Choline acetyltransferase to form ACh again
effect of Curare
binds to AChR so ACh Cannot bind, causing ACh to still be released but not create an AP
where is Curare derived
Plant
effect of Botulinum toxin
blocks ACh release so skeletal muscle activation will not occur
- flaccid paralysis
effectof Organophosphates
Block action of AChE so ACh will not be hydrolyzed
Na channels remain in refractory state
- initially spastic paralysis
- end with flaccid paralysis
Organization of skeletal muscle
whole muscle Fascicle Muscle fiber/cell myofibril Sarcomere Filament Protein
what makes up a thin filament in a muscle fiber
Two intertwined helical chains of actin molecules
what does tropoymosin and troponin associate with and there roll
Tropomyosin wraps around actin to block binding sites on actin
TRoponin is associeted with tropomyosin and binds to Ca to move tropomyosin and expose the binding sites on the tihin filaments
what makes up TRoponin
TnC - calcium binding
TnI
TnT - tropomyosin binding
subunites
what makes up a thick filaments
Myosin moleules
parts of a myosin molecules
Heavy chains
Light chanins
ATP binding sites
Actin binding sites
what is an iosform
same prootein but slightly different amino acid sequence; similar function
the functional unit of the contractile apparatus
Sarcomere
what is a sarcomere made of
Thick filaments
thin filaments
Z-lines
how many sarcomeres are in one muscle
Many
what is found the I band
Titin filament
Thin filament
what is the Titin filament
binds to the z line and the thick filament to elastically pull the sarcomere back together
what is found in the A band
thin filament
thick filaments
M line
what does the Z line bind
titin filament
thin filaments
what is found in the H zone
Thick filaments
M line
what does the M line bind
thick filaments
what is the border of a sarcomere
Z lines
roll of Nebulin
A molecular ruler to determine thin filament length
where is Nebulin found
Thin filament protein
what shape does thick filaments make around a thin filament
a triangle
what shape does thin filaments make around a thick filament
a hexagon
what is Excitation-Contraction coupling
Mechanism by which AP in sarcolemma initiates contraction
what ion has a pivotal role in activation of muscle
Ca
what does Excitation-Contraction copling do to Ca
a rapid and very large increase in free Ca
what binds to Ca2+ in the lateral sacs of the sarcoplasmic reticulum
Calsequestrin
EC coupling steps and release for Ca
- Muscle Action Potential propagate
- Ca released from the lateral sac of the Sarcoplasmic reticulum
- Ca binding to troponin removes blocking action of tropomyosin
- Ca removal from troponin restores tropomyosin blocking action
- Ca taken up by Sarcoplasmic reticulum using ATP
where is Ca ions released from the SR to initiate contraction
from the lateral sacs
what receptor tells the Sarcoplasmic reticulum to release Ca in responce to an AP
DHP receptor on the cell membrane interacting with the ryanodine receptor on the sarcoplasmic reticulum (same receptor allows ca to leave
where is the DHP receptor found
In the transverse tubules of the cell membrane
what makes up the DHP receptor
Ca++ channel and a voltage sensory
what makes up the sarcoplasmic reticulum
Lateral sacs and fenestrated collar
how is Ca ions sequestered/taken up by the sarcoplasmic reticulum
by the fenestrated collar sing the Ca ATPase pump in SR
what is the sliding filament theory
Muscle shortens by a relative sliding of thick and thin filaments
FILAMENTS DO NOT CHANGE LENGTH
what is the cross-bridge theory
thick and thin filaments are not connected at rest
cross-bridges form between the 2 types of filaments following an increase in Free Ca
relation of the cros-bridge theory and the sliding filament theory
cross-bridge theory is the mechanism of the sliding filament thoery
4 stages of Cross bridge cycle
- cross bridge binds to action
- power stroke due to relase of ADP and Pi from thick filament
- ATP binds to myosin and causes cross bridge to detach
- Hydrolysis of ATP energizes cross bridge
what is the amount of force generated by a sarcomere proportional to
number of attached cross bridges
what does the Rate of cross bridge formation determine
rate of muscle shortening
do all types of myosin go through the cycle at the same rate
No at different rates
of the cross bridge cycle, how many steps are attached and detached
2 attached
2 detaches
does a change in ATP concentration occur during muscle contraction and why
No, because the ATP conentration inside muscle cells is buffered by phosphocreatine
what does Phosphocreatine do
donates a phosphate to ADP to create ATP
what is the enzyme that allows PCr and ADP to make ATP
creatine kinase
where is creatine kinase found
at the M line
what are the 3 sources of ATP production
Creatine phophate
Glycolysis
Oxidative phosphorylation
what are the consumers of ATP
Myosin ATPase for contraction
Ca-ATPase for relazation
what is the length-tension relationship
amound of force that a muscle can generate is related to its length
how were the experiments done for the length tension relationship
activate muscle fiber
record tension
stretch
repeat
what is the ratio of how things are used for the sonsumption of ATP
70% contraction
30% relaxation
are thin fibers always the same in different fiber types
LEngths vary for different fiber types
Nebulin vary for differeny fiber types
what does the the observation that a mscle can shorten at a higher veolcity when moving a lighter load
Velocity of skeletal-muscle fiber shortening and lengthening is a function of load
how does the force being sustained by cross-bridges during a lengthening contraction compare to that of a maximum isometric tension
greater than the maximum iosmetric tension (can also lead to muscle injury)
when does the maximum shortening velocity occure
with zero load
when does the maximum isometric tension occur
with zero velocity
formula for power
force x velocity
is the max veolcity the same for all muscles
No, it is different for different types of skeletal muscles
is the curvature of a velocity load graph the same for all skeletal muscle
Differs betwen types of skeltal muscle
is the tension/cross sectional area the same for all skeltal muscle
Relatively constant
isometric
Constant length
Isotonic
constant load
what happens to isotonic twitches as the load increases
slower velocity
lesss extent of shortening
greater latent periods
muscle twitch
recaction of a muscle to one stimuli
what is unfused tetanus
action of a muscle to multiple stimuli
higher tention than twitch but not always at a peak tension (shaking)
what is fused tetanus
lots of stimuli
peak tension and constant
what gives substrates to oxidative phosphorylation
products of glycolysis
fatty acids
oxygen
amino acids from protein (not normal though)
what does the cell use to do glycolysis
GLucose from the blood and glycogen from the muscle fiber
roll of glycogen more than just feeding glycolysis
keeps glucose concentration low in the cell so glocuse diffuses easily in
what is a motor unit
a mingle motoneuron and all of the muscle fibers it innervates
what is a single muscle made of
Many motor units
how many NMJ does a muscle fiber have
one, with one motor neuron
how many muscle fibers can one motorneuron innervate
more than one muscle fiber (100-2000) depending on fine or large movement muscle
are motor units completely separated
no, they are intermingled
how can muscle fiber types be distinguished
Structural (morphological)
Biochemical
physiological critera
what may cause changes in the fibers that comprise a muscle
development disease
exercise
Slow vs Fast fiber NMJ size
slow fibers have smaller SMJ
diamter of slow vs fast muscles
slow fibers are smaller
proteins found in slow vs fast muscle fibers
contain different sarcomere protein isoforms
fatigue of slow vs fast fibers
slow are more fatigue resistant
does the number of muscle fiber we have change after birth
no, but the types may change
what source provides energy for fast fibers
More glycolysis
what source provides energy for slow fibers
More oxidative phosphorylation
type 1 fibers
Slow fiber
types of type II fibers
type IIA
type IIB
size of type IIA vs Type IIB fibers
type IIA are smaller
does TYpe IIA or Type IIB do more oxidative metabolsim
type IIA more oxidative met
are type IIA and IIB more fatigue resitsnat
Type IIA are more fatigue resistant
what contracts slower type IIA or type IIB fibers
Type IIA are slower
what generates more power, type IIA or type IIB
type IIB do more power (faster)
efficiency of type IIA vs type IIB fibers
Type IIB are less efficient
what type of fiber is the most efficient type of skeletal muscle
Type I is the most efficient
what type of fiber is used to maintain posture
type I
what type of fiber is used to do rapid, dexterous task
type II
fatigure resistance of all 3 types of fibers
Type I: resistant
Type IIA: mediu resistant
Type IIB: Fatigue fast
what are som systemic disorders associated with muscle cramps
Dehydration Metabolic Endocrine Pregnancy Drugs/ toxins
metabolic causes of muscle cramps
Low sodium Low Magnesium Low calcium Low Glucose LowPotassium
Endocrine disorders of muscle cramps
Thyroid (hyper or hypo)
Adrenal Insufficiency
what kind of muscle is cardiac muscle similar to
Skeletal muscle
length of cardiac sarcomeres
Not all the same length (possible functional consequences)
what are cardiac sarcomeres composed of
Contractile proteins, that are in some cases also found in skeletal muscle
major difference between cardiac and skeletal muscle
Cardiac has many more mitochondria
size of skeletal vs cardiac muscle cells
Cardiac muscle cells are much smaller
what allows conduction between myosites in cardiac muscle
Gap junctions
benifit of cardiac muscle being different length sarcomeres
different sarcomeres allwyas at the max power potential (w/o would be compromised due to high filling)
what does Skeletal muscle attach to
to tendons
what does cardiac cells attach to
End on end to each other via an intercalated disk
where are gap junctions locaetd
along each intercalated disk
does the heart function as many units
one unit (quick passage of AP’s throughout ventricles
what kind of synapse is found in the herat
Electrical synapses without chemical transmitters for AP transmission
does mature skeletal muscle contain gap junctions
NO
how does cardiac muscle get its energy
OXidative phosphorylation
difference between cardiac muscle twitch and skeletal
cardiac and skelteal have very different tensions and APs for a twitch
Refractory period length of a ventricular muscle cell vs skeltal
Ventricular is much longer(has a plateau period)
200ms vs 3ms
importance of long refractory periods of Ventricular muscle cells
Prevents tetanis contractions (filling of hearting during diastole)
how long does the AP of cardiac muscle last in relation to twitch tension compared to skeltal muscle
Cardiac: AP is until twitch tension is relaxed about 50%
skeletal: AP complete even before the muscle begins to shorten
Stepts of the membrane potenetial of ventricular muscle
depolarizing Repolarization (brief and small) Plateau (long and slow) repolarization (brief and large) Resting
what flows in during the depolarization phase of Ventricular AP
Na flows into the cells
what flow in during the 1st repolarization phase of Ventricular AP
K flows into the cell and Na leaves the cell
what flows during the plateau phase of ventricular AP
Ca flows in and K leaves
what flows during the secondar repolarization phase of ventricular AP
K flows in and Ca leaves
what flows during the resting phase of a ventricular AP
No net current flow
how does Ca get into heart muscle
- Enter cells from interstitial space by passing through channels in sarcolemma during plateau pahse of AP
- these Ca trigger other ca ions from SR that bind to troponin
when Ca entering from the interstiticiul space cause release of Ca from the sarcoplasmic reticulum
calcium-induced calcium release
when does Ca induced calcium release occure
during plateau phase of AP
the primary mechanism for removal of Ca ions from the sarcoplasm
Ca-ATPase pump in the SR (just like that in skeletal muscle
what is responsible for removing Ca out of the cell across the sarcolemma
Ca-ATPase pump
what is the 3rd way to remove Ca from cardic muscle
Na/Ca exchanger moving Na inside cell and Ca out of the cell
does the Na/Ca exchanger use ATP directly
No, uses secondary active transport from the Na concetration gradiant created by the Na/K ATPase
what Ca removal mechansms move the amount of Ca out of the cell equal to the amount of Ca which moves in during the plateau phase of the AP during one contraction and relaxation cycle
sarcolemma Ca-ATPase
Na/Ca exchanger
size of smooth muscle cells
very small (2-10 micrometers in diameter
sarcoplasmic reticulum of smooth muscle
Little SR
are there thick and thin filaments in smooth muscle
Yes, but not identical to skeletal and cardiac muscle
what are the Z line homologes in smooth msucle
Dense bodies
what do thin filaments attach to
Dense bodies
what protein is not expressed in smooth muscle
Troponin
what controls Smooth muscle
ANS (therefore involuntary
what has a greater length range from which force can be generated, smooth or striated muscle
smooth
why does smooth muscle need to contract at larger changes in length
accommodates large changes in volume of organs
rate of ATP splitting by myosin in acivated smooth muscle and what the result of it is
10-100 times lower than skeletal so therefore no fatigue and better econmy
what is the economy of muscle contraction
Force/ATP consumed
what does Calcium bind to smooth muscle
Calmodulin
EC coupling in smooth muscle
- stimulus increases calcium concentration
- caclium binds to calmodulin
- calcium calmodulin complex binds to inactive MLCK to create a Ca-Calmodulin MLCK active complex
- the Ca-Calmodulin-MLCK active causes Pi to bind to myosin leading to contraction
what leads to the relaxed state of smooth muscle
phosphatase causeing Myosin-P to dissociate
when is phosphatase active
caontinuously, but activation results when the MLCK activity is greater than the phosphatase activity
roll of dephosphorylation in Contraction
dephosphorylation prevents reattachment of myosin to actin
roll of ATP in smooth muscle contration
dissociation of myosin from actin as in striated muscle
can dephosphorylated myosin bind actin
no
what happens if myosin bund to actin in smooth muscle is dephosphorylated
remains attached in a rigor state with no movement of the cross-bridges
Result dephosphorylated myosin reamining bound to actin
state of rigor with very little ATP consumption and high economy
source of Ca for activation of smooth msucle
SR
Extracellular fluid
sarcoplasmic reticulum in the Smooth muscle lack
No t-tubules
what does the SR associate with in smooth muscle
Associate with the plasma membrane
how is the SR activated in smooth muscle
that associated with the plasma membrane is released by an AP
non-membrane associated SR activated by second messengers
how does Extracellular fluid Ca enter smooth msucles
from extracellular space through channels in plasma membrane
what causes the rising phase of the AP of smooth msucle
inward flow of positive charge from Ca ions
what is the resting potential of smooth muscle
never steady
do smooth muscles need an neuron to create an AP
Some spontaneously generate APs
what causes membrane potenetial to reach threshold in smooth msucle
Pacemaker potentials
presence of neuromuscular junction for smooth muscle
No NMJ
how does a neuron excite a smooth msucle
endings of motor neurons in ANS release neurotransmitters(excite or inhibit) near smooth muscle
roll of hormones on smooth muscle
neurotrasmitters
what local factors can influence smooth muscle
pH, oxygen level, nitric oxixde, stretch
mechanisms of Ca removal
Ca pump in the sarcolemma
Na/Ca exchanger
SR
types of smooth msucel
Singule unit
Multi-unit
synapse in single-unit smooth muscle
Electrical synapses (gap junctions)
how are single unit smooth muscles active
Spontaneously
how are single unit smooth msucle activated
stretch activated
innervation of single unit smooth muscle
primarily restricted to pacemaker cells
examples of single unit smooth muscle
Smooth muscle in intestinal tract
uterus
small diameter blood vessels
How is multi-unit smooth msucle activated
each cell is activated independently
Not spontaneous
gap junctions in multi-unit smooth muscle
rare
examples of multi-unit smooth muscle
Large arteries
Large airways
