Lecture 11: Functional organization of skeletal muscle & motor units (Hayward) Flashcards
how are skeletal muscle fibers organized?
in motor units
what does each motor unit consist of?
alpha-motoneuron and the muscle fibers innervated by that neuron
where are cell bodies of motoneurons located?
CNS - within the ventral horns of gray matter of the spinal cord or motor nuclei of the brainstem
what does each axonal branch terminate in the formation of?
neuromuscular junction (also called motor end-plate) - the synapse between the axon terminal and the muscle fiber
what are the 3 basic patterns of innervation?
- focal innervation - one synapse per muscle fiber (its the most common form of innervation in mammals)
- distributed innervation - involves 2-5 or more synapses per muscle fiber. this pattern is found in intrafusal fibers, some extraocular muscles and tonic fibers in avian species
- myoseptal innervation - involves pairs of synapses situated near the original and insertion of muscle fibers in some reptiles and vertebrates
describe the presynaptic components of the neuromuscular junction
the axon looses its myelin sheath forming an axon terminal upon reaching the muscle fiber to be innervated
the axon terminal rests in the primary synaptic cleft - a depression on the surface of the muscle fiber.
schwann cells form a covering over the axon terminal
within axon terminals are synaptic vesicles containing Ach
describe the synaptic cleft within the neuromuscular junction
the primary cleft is modified by numerous secondary folds (secondary synaptic clefts or junctional folds) that extend further into the depths of the muscle fiber. this increases the surface area of the sracolemma.
the primary and secondary clefts are filled with external lamina that contain acetylcholinesterase (AchE) which is an enzyme that hydrolyzes Ach to acetate and choline
describe the postynapptic components of the neuromuscular junction
on the crests of the junctional folds are acetylcholine receptors (nicotinic receptor type). these are transmembrane ligand-gated receptor ion channels that upon activation open and increase membrane permeability to Na and K.
what does neuromuscular transmission involves events associated with what?
the formation of a muscle action potential initiated by a nerve action potential
what are the events associated with neuromuscular transmission?
- nerve action potential
- Ca uptake
- Ach release
- Diffusion of Ach
- formation of end-plate potentials
- muscle action potentials (MAP)
describe the nerve action potential
its an impulse originating at the motoneuron cell body and is conducted along the axon to the axon terminals
what is the effect of Ca uptake in neuromuscular transmission?
with the arrival of an action potential at the axon terminal, Ca ions enter the axon terminal via voltage- gated Ca ion channels
how does the release of Ach into the synaptic ceft occur in neuromuscular transmission?
calcium ion dependent exocytosis
what is the end-plate potential (EPP)
it is a local membrane potential created when two molecules of ACh reversibly bind to the ACh-receptor resulting in increased permeability to Na and K.
these changes can initiate muscle action potentials
how does the action of ACh terminate
with its disassociation and diffusion away from ACh receptor and its hydrolysis by AChE.
what is the miniature end-plate potential (MEPP)
in the absence of nerve action potentials at the neuromuscular junction, there may be a spontaneous process of single vesicle release of ACh that forms a small local membrane potential called the miniature end-plate potential.
it is insufficient to initiate muscle action potentials
describe the muscle action potential (MAP)
when the end-plate potential (EPP) reaches a critical level, a MAP is generated from the end-plate and propagated out over the sarcolmma in all directions.
within the T-tubules, the MAP initiates Ca release from the SR
define electromyography (EMG)
it involves the detection and characterization of electrical activity (MAP) recorded from the patient’s muscles.
its usually conducted with their muscles at rest - not contracting.
what is an expected result from a normal EMG?
muscles at rest should be electrically SILENT
what could be indicative of neuromuscular diseases in an EMG?
increased insertional activity
affected muscle fibers may be hyperexcitable, having a lower threshold
sponatenous activity may also be observed independent of mechanical stimulation
this activity may be associated with delayed relaxation of the muscle or exaggerated spontaneous release from the nerve ending.
what does motor nerve conduction velocity tell you
it provides information on the integrity of nerve fibers in peripheral nerves
what are evoked potential recordings
repetitive nerve stimulation provides information about the integrity of neuromuscular transmission
what are 3 presynaptic disorders?
- hypocalcemia
- hypercalcemia
- botulism
hypocalcemia
exocytotic release of Ach from axon terminal is calcium ion dependent.
In hypocalcemia, there is a reduced Ach release associated with muscle weakness.
hypercalcemia
increased Ach release associated with weakness due to continued depolarization of post-synaptic membrane
botulism
toxin irreversibly binds to presynaptic membrane and blocks release of Ach. results in a functional denervation of all muscle fibers
what is myasthenia gravis (MG)?
a deficiency of Ach receptors on postsynaptic membrane. it is an aquired (immune mediated) neuromuscular disorder in dogs.
it is typically observed in dogs older than 1 year.
what will an EMG of a dog with myasthenia gravis show?
a progressive decline in evoked potentials evoked by repetitive nerve stimulation
how do you treat dogs with myasthenia gravis?
tx involves improving neuromuscular transmission through the use of cholinesterase inhibitors and/or suppression of immune response with steroids.
what is X-linked muscular dystrophy of dogs and cats
its a hereditary myopathy in which there is a deficiency of dystrophin, which is a cytoskeletal protein associated with the inner face of the sarcolemma of all the muscle fibers.
this is a genetically-linked deficiency which has been well characterized in golden retrievers.
what would an EMG of a dog with X-linked muscular dystrophy typically show?
repetitive, high frequency discharges
the contractile responses of muscles are usually studied ine 1 of 2 possible recording conditions - what are they?
isometric contractions
isotonic contractions
how are isometric contractions recorded?
with the origin and insertion of the muscle fixed so that length of muscle remains constant during recordings
define Lmax
the length at which a muscle develops its maximum tension
what happens when a muscle is set at lengths shorter or longer than its resting length?
the tension it can develop will be less than when set at its resting length
how are isotonic contractions recorded?
with the tendon of origin fixed while the tendon of insertion is connected to a load that is lifted during shortening.
describe the force-velocity relationsip
with increased velocities of shortening, the number of cross-bridge interactions is increased thereby decreasing the number of actin-myosin bonds present at any given time.
meaning that during high velocities of shortening only low forces may be lifted
what is an example of isometric contraction?
fixation of joints while standing
what is an example of an isotonic contraction
flexion or extension movements of bony segments
what are twitch contractions?
responses to a single applied stimulus and are composed of a phase of developing tension following by phase of relaxation and diminishing tension.
how do you measure the ‘speed’ of contraction?
through contraction time (Tc) which is the time required for the tension developed to reach maximum (peak) tension.
fast contracting muscles have shorter contraction times than slow muscles
what is the Active State of muscle?
the time course and magnitude of the contractile/chemical events associated with the interaction of the myofilaments
what is the difference in timing of the active state vs the mechanical events? what is this difference due to?
the observed magnitude and time course of the mechanical events at the level of the whole muscle lag behind the active state.
this is due to the fact that the internal elastic components must be stretched before force production is transferred to the tendons of the muscle.
what must a muscle overcome during contraction?
a muscle must overcome the “slack” (elasticity) and viscous properties of these elements before the full effects of contraction can be realized.
what happens with increasing rates of repetitive stimulation to muscle? how does this occur?
the tension developed is additive.
this occurs because previous twitch contractions stretched out internal elastic components allowing subsequent contractions to devote less time in the active state stretching out components and more time producing force on the muscle tendons.
what happens at tetanus (Po)?
viscoelastic elements are overcome and the true maximum contractile tension capability is realized
what is fused tetany?
a maximum tetanic contraction
what is fusion frequency?
stimulation frequency
what fusion frequency is needed to reach fused tetany?
its related to the twitch contraction and relaxation time.
the slower the twitch contraction time, the lower the stimulation frequency needed to reach a fused tetanic contraction.
what is an unfused tetanic contraction
stimulation frequencies below the fusion frequency
what are slow-twitch (S, Type I) motor units
contraction times are relatively slow (60 - 70ms)
tetanic fusion frequency is relatively low in type I motor units
- resistant to fatigue
- able to maintain their tetanic tensions for relatively long periods without fatigue (30 - 60 minutes)
what are fast-twitch (F, Type II) motor units
contraction times are relatiely fast (30 - 40 ms)
tetanic fusion frequency is relatively high
what are the two different fast-twitch type II muscle types regarding fatigue and define them
fast-twitch, fatigue resistant (FFR, type IIA) motor units - relatively resistant to fatigue and are able to sustain their tetanic tensions at 75% of maximum for 5ish minutes
Fast-twitch, fatigable (FF, Type IIB) motor units - cannot sustain tetanic tensions above 25% of maximum for more than 1 - 2 minutes.
describe speed of contraction as a property of myofibers
the shortening of sarcomeres is directly proportional to the actin activated ATPase activity of myosin.
the myosin ATPase activity of myofibers in FF and FR motor units is greater than the myosin ATPase activity of S motor unit fibers
describe the myosin ATPase activity differences between type 1 fibers and type 2 fibers
type 1 fibers (slow twitch) have a low myosin ATPase activity and stain lightly histologically
type 2 fibers (fast twitch) have a high myosin ATPase activity and stain darkly
which two muscle types contain high numbers of mitochondira
Type I myofibers (slow twitch) and Type IIA myofibers (fast twitch fatigue resistant)
which type of myofibers generate more force? why?
type 1 - slow twitch because they have a grater total cross-sectional area
explain the homogeneity of motor units
each motoneuron innervates only 1 type of muscle fiber (either type 1 or type IIA or type IIB)
what is the order recruitment of motor units?
with minimal and sustained activity - type S and type FR units are recruited first
Type FF units are the last to be recruited and only work for a short duration on high intensity activities.
what is the size principle?
the orderly recruitment of motor units within the CNS
