Skeletal Muscle Flashcards
whats a graded potentials
graded potentials are changes in membrane potential that are cinfined to a small region of the membrane (local AP)
what happens when a graded potential occurs
- > charge flows between the origin of the potential and adjacent regions of the membrane that are still at resting potential
- > membrane channels are briefly opened and a potential that is less negative than at rest will occur
- > positive charges on the inside of the cell will move to areas that are more negative and away from the depolarized area, positive charge will flow towards the depolarization site
- > the charge is eventually lost across the membrane (since membranes are leaky to ions so that the change in membrane potential is lost the further you move from the initial site of depolarization)
the magnitude of the graded potential is dependant on what?
magnitude f the initiating event
- > graded potential can result in a full membrane AP if the initial graded potential is strong
action potential propagation
how each action potential that occurs at a location on a membrane/neural axon results in ion flow across the membrane and can result in depolarization of the adjacent membrane
describe action potential propagation in neural cells
in neural axons, there is a sequential opening and closing of Na and K channels along the length of the axon, the AP doesn’t move but it sets off a new AP in the region of the axon ahead of it
the velocity of neuronal axon AP propagation depends on what
- fibre diameter
- > the bigger the fibre, the faster the conduction of the AP along the axon - fibre myelination
- > myelination increases the speen of AP propagation
MS
acute myelin breakdown with formation of lesions or plaques on the neural axon
characteristics of an AP at different parts of the neural axon
AP only occur at the node of Ranvier (where the myelin coating is interrupted and the conc. of voltage gated Na channels is high)
- > therefore AP literally jump from node to node as they propagate along the axon (saltatory conduction)
- conc. of voltage gated Na channels is low in the myelinated regions of the axon
Conduction Velocities
Small diameter, non-myelinated fibres
- > 0.5m/s (4 secs for a signal to go from the toe to the brain
Large diameter, myelinated fibres
- > 100m/s (0.02 secs from toe to brain)
Steps of an Action potential
- CNS sends a signal to the motor neuron, which results in the opening of Na channels in the sarcolemma
- muscle cell membrane potential is altered as Na floods into cell
- AP travels along sarcolemma
- AP travels down the T-Tubules
- integral membrane protein in the T-tubules (dihydropyridine, DHP receptor) acts as a voltage sensor noting the action potential
- DHP receptors undergo a conformational change, resulting in the opening of the ryanodine receptor calcium channels in the SR membrane
- Na channels in the sarcolemma close and K channels open; Na-K pumps bring the membrane potential back to resting levels
- Ca floods out of the SR and into the cytosol
- Cross bridge cycle starts
- contraction occurs
- calcium is actively pumped back into SR
2 classes of synapses and where are they found
- Electrical
- > found in cardiac and smooth muscles - Chemical
- > found in skeletal muscles and nervous system
relate excitatory and inhibitory synapses to chemical synapses
in general, both excitatory and inhibitory synapses can occur, however, there is no inhibitory activity at the neuromuscular junction
- > skeletal muscles can therefore only be excited
describe an excitatory synapse in a skeletal muscle
at an excitatory synapse, the release of the neurotransmitter results in post-synaptic depolarization through the opening of Na, K and/or other small ion channels as a result of an activated receptor
why do chemical synapses on do one-way conduction
the neurotransmitter is stored on the pre-synaptic side and the receptors are found on the post-synaptic side
motor end plate
the region of muscle cell directly under terminal endings of axon
terminal endings
ends of axon embedded into grooves on a muscle cell
- > contains vesicles
- theses vesicles contain acetylcholine, a neurotransmitter
neuromuscular junction
motor end plate + terminal ending
steps to neural initiation of muscle cell AP
- AP travel down neural axon
- AP reaches axon terminal (Na influx)
- AP (depolarization) of the axon terminal results in the opening of Ca channels in the neural axon plasma membrane
- Ca floods into axon terminal from extracellular fluid and acts as a neural transmitter
- causes exocytosis of vesicle and release of acetylcholine into the extracellular cleft
- Ach binds to receptors (nicotinic - > G-protein activation) on the motor end plate
- causes Na channels to open
- Na floods into the cell
- Causing the local depolarization of motor end plate occurs (EPP= end plate potential)
10 AP spreads from motor end plate spreads to rest of sarcolemma - Ca is released from SR
12 Contraction (cross bridge cycle
motor end plate also contain ____
acetylcholinesterase
- > an enzyme that breaks down acetylcholine
What happens when acetylcholinesterase breaks down Ach
- > as [Ach] decrease (due to breakdown), less Ach is available to bind to the motor end plate ach receptors which causes the closure of ion channels in the motor end plate (ends contraction)
- > depolarized motor end plate membrane returns to resting potential (repolarization)
List all diseases/drugs that can modify the events at neuromuscular junctions
- Curare
- Organophosphates
- Clostridium Botulinum
- Rigor mortis
- Sarin
- Rocuronium
- Succinylcholine
curare
- > binds to Ach receptors on the motor end plate but does not allow ion channels to open (antagonist to Ach activity)
- > no AP is generated in the muscle and death can be through asphyxiation due to lack of contraction of the respiratory muscles
- > it was once used in surgery in small amounts to stabilize muscles during incisions
organophosphates
(nerve gas, certain pesticides)
- > inhibit the actions of AchASE such that ion channels remain open and the membrane cannot depolarize
- > COD asphyxiation due to resp. muscle paralysis
clostridium botulinum
release botulinum toxin (botox) that breaks down the protein required for the release of Ach from the neural axon and therefore, preventing initiation of muscle contraction
rigor mortis
stiffening of the skeletal muscle after death
- > caused by the flood of Ca from stores and a decline of ATP
Sarin
nerve gas that inhibits AchASE, resulting in a buildup of Ach in the synaptic cleft
- > this results in over-stimulation and uncontrolled muscle contraction
- > receptor desensitization to Ach will quickly occur and muscle paralysis results
rocuronium
neuromuscular blocker that is an antagonist at the neuromuscular junction
- > used for surgery and tracheal intubation
succinylcholine
binds to the sarcolemma Ach receptors but is resistant to degredation by AchASE
- > holds the membrane in the depolarized state
muscle tension
force exerted on an object by a contracting muscle
load
force exerted on a muscle by the weight of an object
what happens if muscle tension is greater than load
then the load can be moved
forcefulness of the muscle contraction depends on what
depends on the length of the sarcomeres before contraction begins
when do muscle fibres develop the greatest tension
when there is an optimal overlap between thick and thin filaments
- > i.e. the greater the number of myosin heads that are aligned to the thin filaments, the greater the sarcomere shortening
what are the conditions of a muscle fibre for no contraction/tension to occur
a muscle fibre has to be stretched in such a way that there is no overlap between thick and thin filaments
what happens if a muscle fibre is shorter than optimum length
tension decreases because the thick filament deforms and the myosin head cannot attached to the thin filaments
isotonic contractions
muscle fibre tension remains constant as the muscle fibre changes length
isometric contractions
when the muscle fibre is prevented from shortening so tension develops at a constant muscle fibre length
concentric contraction
dynamic form of isometric contractions that produces tension during a shortening motion
- > i.e. weight lifting
eccentric contraction
form of isotonic contraction that is also known as a lengthening contraction
dynamic contraction
also known as a changing-force contraction due to the chances in the force exerted by a muscle as it shortens
static contractions
a muscle contraction that produces an increase in muscle tension but does not result in change in limb or joint displacement
single-muscle fibre contraction
a single AP that results in a single muscle cell contraction (twitch)
three steps of twitch contraction
- AP
- latent potential
- contraction time
latent period
processes associated with excitation-contraction coupling (neuromuscular activation) occur during this period
contraction period
time from the beginning of tension development to peak tension
- > duration of contraction time depends of the time that cytosolic Ca levels remain high and is related to Ca-ATPase activity in the SR.
frequency-tension relation
because AP takes significantly less time than a twitch, it’s possible to have a second AP activate during a period of mechanical activity, enhancing the response
tetanus
muscle fibre is stimulated at a frequency that prevents relaxation between stimulation
- > contractile activity is sustained (until fatigue)
unfused tetanus
longer time between stimulations (lower frequency) allows for partial relaxation of the muscle fibre between stimulations = oscillation
fused tetanus
higher frequency of stimulations so no oscillations occur
maximal tetanic tension
point where stimulation frequency is so high that increased tension no longer occurs
- > MTT means fibres have shortened maximally and there is no more ability for actin-myosin binding
What occurs with tetanic contractions
- > Ca is released from the SR by the initial AP
- > 2nd, 3rd, 4th, ect, APs continue to stimulate the release of Ca from SR so that even the pumping of Ca back into SR, cytosolic levels of Ca remain high so that troponin can become saturated and A-M can bind
can a single twitch initiate maximal fibre tension
maximal fibre tension does not develop due to the rapid pumping of calcium back into SR before all myosin-actin can bind
- > therefore with single twitch, Ca is removed from actin/troponin sites before maximum tension develops
velocity
refers to the speed/velocity of the shortening of the sarcomere
2 isoforms of the creatine phosphokinase enzyme are found where and with who
one in skeletal muscle
- > skeletal form of the enzyme is found to be elevated in patients with MD (muscular dystrophy)
other in cardiac muscle
- > cariac muscle form is elevated in people that have had an MI (myocardial infraction/heart attack)
where does creatine come from
come from the breakdown of dietary proteins
what happens when you take creatine supplements
you can increase body storage of CP by around 20% but there is a limit to how much can be stored
- > kidneys may be affected with the high flow-through creatine
which metabolic system produces the most ATP for contractile activity
oxidative phosphorylation
muscle fatigue
the amount of muscle fatigue is related to the type of muscle used and the type and duration of the exercise
repeated stimulation of muscle fibres causes ___
- decreased tension development
- decreased velocity of shortening
- rate of relaxation
impact of metabolic changes on muscle fatigue
metabolic changes can result in alterations to normal skeletal muscle fibre activity such as:
- > decreased rate of calcium release, re-uptake and storage in the SR
- > decreased sensitivity of the thin filament proteins to activation by calcium
- > inhibition of the binding and power stroke motion of the myosin cross-bridge
types of fatigue
- Central Comand fatigue
2. Peripheral fatigue
Central command fatigue
- > occurs when appropriate regions of the cerebral cortex fail to send excitatory signals
- > possibly due to the inhibition of voluntary effort in the CNS and/or malfunction of motor neurons due to physiological changes (i.e. inc core temp, build-up of toxic metabolic waste
where does peripheral fatigue happen, why
- Neuromuscular junction
- > may be due to depletion of neurotransmitters, Ca, ATP - Skeletal muscle fibres
- > depletion theory
- > accumulation theory
- > conduction failure
- > inhibition of Cross-bridge cycle
- > ryanodine receptor regulation alteration
explain the depletion and accumulation theories
deletion (looks at prolonged exercise)
- > depletion of ATP, PC, glycogen may result in muscle fatigue
accumulation
- > accumulation of metabolic by-products (such as H, NH, PO) may have deleterious effect of muscle
explain conduction failure
- > the muscle AP can fail to be conducted into the fibre along the T-Tubules halting the release of calcium
- > may be due to the buildup of K ions in the t-tubules as a result of repetitive APs
- elevated K levels result in persistent depolarization of the membrane and inactivation of the Na channels `
inhibition of cross-bridge cycling
- > the buildup of ADP and Pi within muscle fibres during intense activity may directly inhibit or slow cross-bridge cycling
- > slowing the rate of cross bridge movement can delay cross-bridge detachment from actin
- > reduced shortening velocity and impaired relaxation can occur
ryanodine receptor regulation alteration
- > during prolonged exercise, ryanodine receptors become leaky to Ca maintaining a persistent, elevated cytosolic calcium concentration
- > although high cytosolic levels of calcium can maintain contraction, persistently high levels can degrade contractile proteins
- contractile protein degradation = fatigue, loss of contractile strength, muscle soreness
muscle regeneration
recovery from muscle injury requires divergent responses from macrophages
M1 macrophages promote inflammation and proliferation of muscle-resident stem cells (satellite cells)
M1 then switch to M2 cells that decrease the inflammation and promote sat cell differentiation
skeletal muscle fibre types
Contractiles Properties - > slow twitch fibres - > fast twitch fibres Metabolic properties - > slow oxidative fibres - > fast glycolytic fibres - > fast oxidative glycolytic fibres
slow twitch fibres
- > innervated by alpha2 motor neurons, these neurons tend to be small with a slow conduction velocity
- > known as type 1 fibres
- > have relatively low myosin ATPase activity
- > low excitatory thresholds and tend to be activated when low force output is required
fast twitch fibres
- > innervated by alpha1 motor neurons- these neurons are large with a fast conduction velocity
- > these fibres contain myosin with high myosin ATPase activity
- > also known as type 2 fibres
- > tend to have a higher excitability threshold and tend not to be activated until high force output is required
slow oxidative fibres
mainly slow twitch fibres which rely on oxidative metabolism to supply energy
- > low myosin ATPase activity
- > slow maximal shortening velocity
- > high oxidative capacity with large concentrations of oxidative enzymes, myoglobin, glycerides and mitochondria
- > atp produced dependant on blood delivery of oxygen and fuel molecules
- > very resistant to fatigue
fast glycolytic fibres
- > composed of fast twitch fibres that perform primarily under glycolytic conditions
- > high myosin ATPase activity
- > high glycolytic activity (high conc. of glycolytic enzymes and glycogen stores)
- > few mitochondria, low capillary activity and low conc. of myoglobin
- > fatigues rapidly due to relatively low numbers of ATP formed though glycolysis
fast oxidative glycolytic fibres
- > composed of fast twitch fibres that have the ability to work under oxidative and glycolytic conditions
- > high glycolytic activity with high conc. of glycogen and phosphocreatine
- > intermediate oxidative enzyme activity with intermediate conc. of capillaries, myoglobin, mitochondria and triglycerides
- > intermediate susceptibility to fatigue
a whole muscle is made up of ____
motor units
motor unit
a motor neuron + muscle fibres innervated by that neuron
- > a single motor neuron can innervate a few thousand muscle fibres
each motor neuron is composed of what
- > ST/SO motor units
- > FT/FOG motor units
- > FT/FG motor units
- > whole muscle has the three different motor units
- proportions differ based off the muscle
single-fibre contractions vs whole muscle contractions
Single fibre
- > tend to be all or nothing
Whole muscle
- > can be graded (in intensity) depending on the amount of force that needs to be developed
the tension development of a whole muscle depends on what
- amount of tension developed in each fibre
- > depends of the type of fibre making up the muscle - number of fibres contracting (which depends on..)
- > number of fibres per motor unit
- > number of active motor units
relate the size of the diameter of the muscle fibre to force
in whole muscle, the greater the diameter of the fibre, the greater the force
what happens when more muscle tension is needed
more motor units are recruited
*recruitment = increasing the number of active motor neurons
different types of exercise
- > low-intensity, long duration exercise
- > short duration, high-intensity exercise
what happens during low intensity, long duration exercises
- > (in fast and slow oxidative fibres) increased mitochondria
- > increased capillaries
- > slight decrease in fibre diameter (decreased muscle fibre nutrient needs)
- > increased endurance (through increase oxidative pathway usage)
- > slight decrease in muscle strength
what happens during short duration, high intensity exercise
- > increased fibre diameter (increased number of sarcomeres for inc. force/tension
- > inc. glycolytic enzymes (dec. dependancy on O2 for ATP prod)
- > inc. muscle strength
- > decreased endurance (due to glycolytic usage)
other muscle adaptations
- Denervation atrophy
- > in neurons from muscles are destroyed, muscle fibres become progressively smaller in diameter and contractile proteins levels will decrease (dec. tension and inc. weakness) - Disuse atrophy
- > muscle fibres become smaller when muscle is not used for long periods of time - hypertrophy
- > increase in muscle fibre size due to exercise (along with changes in chemical composition - age atrophy
- > decreased muscle fibre size with aging and decreased ability of a muscle to adapt to exercise
motor movement is controlled by input from which areas
- > afferent neuron terminals at the level of the spinal cord
- > the primary motor cortex
- > brainstem nuclei
`motor program
the middle level takes the information from the receptors and forms a motor program which is then sent to the local levels (brainstem) and exits via the spinal cord
parkinsons disease
- > degenerative disorder of basal ganglia/nuclei function resulting in destruction of the nigrostriatal pathway along with decreased synthesis and release of dopamine
- > loss of dopamine can result in unchecked activity of Ach
- > muscular effects can result in tremors, rigidity, bradykinesia
ALS
amyotrophic lateral sclerosis
- > progressive degeneration/destruction of motor neurons
- > reuslts eventualy in loss of skeletal muscle activity, including muscles of the respiratory system
