BIO 409 midterm 2 objectives

Describe the basic characteristics and goals of endurance training; provide examples of activities that are considered endurance training activities.

-increase in fatigue resistance -long term exercise -marathon running or swimming

state the effect of disuse on force output and twitch duration in a postural muscle (e.g., soleus) during both max twitch and tetanus; in rat muscle did they see the same effect in the gastroc muscle? (slide #6)

Force output decrease after disuse. twitch force decreases and titanic force decreases increased fatiguability disuse causes increased connective tissue soleus have a greater decrease than gastroc because its postural

Describe the location, anatomy and function of a golgi tendon organ.

Golgi tendon organs -respond to tension during contraction (mostly isometric) -triggers a relaxation reflex (inhibition reflex) that prevents muscle damage 1. neuron from golgi tendon organ fires 2. motor neuron is inhibited 3. muscle relaxes 4. load is dropped

Describe the main forms, causes and underlying mechanisms of muscle damage.

In almost all cases of skeletal muscle injury there is an attempt at regeneration 1. Muscle strain -pulled muscle, tearing or damaging muscle fibers that results from overstretching 2. muscle soreness- DOMS exact mechanism is unknown, possibly ue to increased Ca 2+ in the muscle fiber that came from the interstitial fluid via minute tears in the plasma lema related to increased lactate production during activity -worse for novel exercise or eccentric contraction 3. muscle cramps -probably due hyper excitability of somatic motor neuron, leads to increase stimulation of muscle

State the main elements that will lead to a) increased force and b) increased speed, and c) increased power; verbally explain, graphically draw and use mathematical equations to describe the relationship between force and shortening velocity of muscle.

Increased Force -increase in cross sectional area -motor unit recruitment -increaed pentagon angle Speed at a given load -increased sarcomere # (fiber length) -decreased pentagon angle -transformation to faster MHC composition To increase power you might increase force, speed or both the most effective way to build muscle bulk and force is small numbers of high force contractions (resistance training)

Be able to describe and draw both a monosynaptic and polysynaptic pathway; describe the role of the interneuron (excitatory or inhibitory) in a polysynaptic pathway.

Monosynaptic reflex stimulus>recptor>sensory neuron>efferent neuron> target cell effector >response has a single synapse between afferent and efferent neurons Polysynaptic refex stimulus >receptor >sensory neuron> interneuron> effecent neuron>targer cell effector> response polysynaptic reflexes have two or more synapses

Describe the process of post-natal muscle growth (both growth in length and girth); State the factors/stimuli that influence muscle growth

Muscle increase in length- by the addition of new sarcomeres to the ends of fibers grith- bu the enlargement and subsequent splitting of myofibrils to create new myofibrils in the fiber muscle size at any point in time reflects the balance between muscle protein synthesis 9anabolism) and breakdown (catabolism) Stimuli that affect post natal muscle development, growth and plasticity -hormones -growth factors and cytokines -mechanical factors -nutrition

Explain in detail the cellular level regulation of muscle plasticity that occurs during endurance or resistance and training; be able to state the coactivators involved, the specific effects of these coactivators and the mechanism by which they exert their effect.

PGC1 is a coactivator that interacts with transcription factors to activate transcription from specific sets of genes Endurance exercise - increase in PGC-1a1 >>> increased -MHC1 and IIa -mitochondria -FAO -VEGF Resistance training -increase in pGC 1a4 leads to -decreased myostatin -increased IGF-1 different types of exercise increase the expression of different PGC-1a isoforms leading to different changes in gene expression Myostatin=negative regulator of muscle wroth -stops uncontrollable growth

anatomy (including fiber size, mitochondrial density, myoglobin concentration, capillarity, etc...) - force generating ability

SO -more mitochondria -small -more myoglobin -more cappilaries -highest O2 demand FG = opposite larger with more myofibrils= more force generating ability

compare and contrast specifically how each fiber types differ in their: o shortening velocity - state what determines the shortening velocity. - describe the effects of body size on shortening velocity.

SO <FOG<FG each muscle type uses a different MHC isoform which makes myosin faster at hyrdolyzing ATP -contraciton velocity is dependent on MHC iosform smaller animals have faster shortening velocities bigger animals tend to move more slowly

Define a 'motor unit', describe its anatomical structure, and fiber type dynamics

a nerve is a bundle of somatic motor neurons a motor unit is 1 neuron and all the muscle fibers it innervates axon terminals attach to muscle cells at euro muscular junction axons of motor neurons extend from the spinal cord to the muscle. Each axon dived into a number of axon terminals that form NMJs with muscle fibers scattered throughout the muscle Recruitment= telling multiple motor until to contract -more stimulus =more motor until being recruited -once they all fire= max contraction

Explain or draw the difference between a pennate and a strap/parallel/fusiform muscle; correctly identify or draw a graphical comparison of the 'force-velocity' and 'length tension' curves between a pennate and parallel muscle.

a pennate muscle produces more force but has a decreased shortening velocity parrelel = faster but less force velocity- V sarcomere*cos theta* # sarcomeres pennate muscles short fibers with larger PCSA F vs L graph higher peak, that doesn't go as far because it doesn't have as much length as a parallel muscle F vs velocity graph Pennate muscle starts higher because more force is produces at 0 and very slow velocities declines much more quickly than a parallel muscle i.e. can produce more force at slow contraction speeds but as soon as contraction starts speeding up parallel muscles produce more force

State and draw the neuronal pathway of a muscle spindle's reflex pathway; describe the function of the stretch reflex

at rest -spindles are tonically active firing even when muscle is relaxed 1. extrafusual muscle fibers at resting length 2. sensory neuron is tonically active 3. spinal cord integrates funciton 4. alpha motor neurons to extrafusal fibers receive tonic input from muscle spindles 5. extrafusal fibers maintain a certain level of tension even at rest muscle fibers can trigger a stretch reflex 1. muscle stretches 2. increased afferent signal to spinal cord 3. spinal cord 4. increased efferent out through alpha motor neurons 5. muscle contracts firing rate of afferent sensory neurons decreases via negative feedback

Describe the process of motor unit recruitment and its effect on force output, 1) the relative synchronistiy/asynchronisity of recruitment, 2) the temporal pattern of recruitment in regards to fiber types, 3) the typical number of motor units in a muscle and the number of fibers in a motor unit, 4)the effects of motor unit number/size on muscle function/activity 5) the spatial distribution of motor units within a muscle group.

recruiting more motor units increases force production 1. not all motor units contract simultaneously, asynchronous contraction helps prevent fatigue, spreads the load 2. motor units are spread out in muscles not in clusters slow oxidative fibers are recruited first, then FOG then FG 3/4. 100-4000 motor units/cell 5-2000 cells/unit the more motor units there are the more fine tuned movement can be-hands and eyes vs but and legs -the fewer muscle cells a unit innervates also goes a long with very fine tuned movements -if each motor neuron only innervates a couple cells you have the potential to move very few cells at a time=soft/fine movement 5. motor units are evenly distribute in muscle groups they are not in clusters each motor unit only innervates one fiber types ex: motor neuron A only innervates slow twitch fibers which are spaced evenly throughout the cell amount of force generated depends on the fiber type in the motor unit that is recruited so<FOG<FG first small force then medium then big if required biggest force uses the most energy and is only used when necessary

Define myoglobin, state its basic molecular form, its location in the body and its functional role.

skeletal muscle contains myoglobin, an O2 binding pigment acts as an O2 sponge darker meat has more myoglobin sequesters O2 effectively lowering partial pressure of oxygen in cells allowing diffusion of O2 down its concentration gradient

draw how the force-velocity curve would change for a muscle/fiber following disuse; predict how the power (Y-axis) by velocity (X-axis) curve would change between use and disuse

the force velocity curve is shifted down after disuse. less power at the same velocities the power velocity curve would probably also shift down. less power can be produced at all the same velocities

State the benefit of muscle tone.

the stat of partial contraction maintains optimal resting length which means max tension can be produced ' body naturally has optimal resting length of sarcomeres>force optimization

List and describe alternate (non-twitch) patterns of skeletal muscle innervation by motor neurons, describe the nature of the potentials and contractions in these types of muscles, as well as identify where they can be found.

vertebrate tonic muscle fibers- have multiple synaptic contacts by a single motor neuron. (1 motor unit touches a muscle cell in multiple places) Tonic fibers do not produce action potentials (just graded potentials) Rare in lower vertebrates and found in humans in eye muscles no action potential, just graded depolarization Arthropod muscle fibers- each fiber is innervated by more than one motor neuron: Poly neuronal innervation Arthropods also have multiple NMJ's/cell Both have graded muscle contractions in a single fiber. The more stimulus the more synapses will be stimulated this can create summation in a single fiber and produce a graded response.

describe in detail the benefit of having multiple different fiber types, rather than a single fiber type that carries out all kinds of muscle activity; a complete description should be able to include graphs if necessary.

we have different muscle fiber types because they are good at different things -functional advantages -at any speed type II produces more force -type II fibers use more energy/area of muscle than type I at any given speed -Type I are more efficient at slow speeds -type II more effcient at faster speeds this means we can conserve energy -if we used type II all the time it would be a waste of energy - we evolvoed to do a wide range of activities using minimal ATP

problems with calcium release and reuptake

with fatigue force output decreases -calcium concentrations align with force output -strong evidence calcium release is related to fatigue -caffeine causes increased calcium release -force of a twitch is recovered with caffeine

Glycolysis: § where does the glucose come from? § for a single glucose molecule what is produced during glycolysis? what is used up? § what are the regulatory enzyme of glycolysis? § where does glycolysis take place? § as a standalone process what is the functional (energetic) importance of glycolysis? § strictly speaking, does it require oxygen?

-Glucose comes from food -single molecule produces 2 pyruvates, 2 NAD reduced to 2 NADH2, 2 ATP (NET) -Hexokinase, phosphofrunktokinase, pyruvate kinase -cytosol -takes place more quickly than krebs -no

Explain the process and functional benefit of alpha-gamma coactivation; explain the outcome of failing to elicit this response.

-alpha gamma coactivation maintain spindle function when muscle contracts 1. alpha motor neuron fires and gamma motor neuron fires 2. muscle and intrafusal fibers both contract 3. stretch on centers of intrafusal fibers unchanged. firing rate of afferent neuron remains constant -without gamma motor neurons, muscle contraction causes the spindle firing rate to decrease 1. alpha motor neuron fires 2. muscle contracts 3. less stretch on center of intrafusual fibers 4. firing rate of spindle sensory neuron decreases

Krebs Cycle: § what fuel molecules (macromolecules) can be used to power the Krebs cycle? § for a single glucose molecule what is produced during the Krebs Cylce? what is used up? § what are the regulatory enzyme of the Krebs cycle? § where does the Krebs cycle take place? § as a standalone process what is the functional (energetic) importance of the Krebs cycle? § strictly speaking, does it require oxygen?

-can be powered with fatty acids, proteins or pyruvic acid (from glycolysis) -8 NADH2, 2 FADH2, 2ATP equivalents -pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase -mitochondria -? -no

Summarize the main effects of disuse on skeletal muscle.

-decreased muscle mass -cell fiber atrophy -increase in connective tissue -decrease in proportion of type I (SO) fibers Type I>typeII -decreased twitchand titanic in human and animal voluntary (human) force due to decreased ability to fully recruit motor units -increased fatiguability -extra junctional ACh receptors and axon terminal sprouting/degeneration

List the known features of muscle during DOMS (delayed onset muscle soreness); identify a muscle as having experienced DOMS based on a TEM image

-disruption to sarcomeric organization and contractile proteins -micro tears in the plasmalemma -swelling and disruption of sarcotubular system -necrosis -infiltration of mononuclear inflammatory cells of the immune system -presence of central nuclei -sarcoemeres look all jagged and stretched out

State the effects of endurance training on: a. capillary density i. state the factor that stimulates angiogenesis. b. mitochondrial density c. lipid droplet concentration d. myoglobin concentration e. resistance to fatigue i. describe why endurance trained muscles are more resistant to fatigue. f. concentration and activity of oxidative enzymes (e.g., Krebs cycles enzymes and fatty acid oxidation enzymes)

-increase in capillary to fiber ration 1. more capillaries (increased density) -VEG-F vascular endothelial growth factor triggers capillary production (VEGF triggers capillary increase) -staining a cell with SDH shows increase in mitochondria and oxidative enzymes after 12 weeks of treadmill running 2. increase in mitochondria 3. increase in lipid droplets in muscle -fuel source for endurance activity 4. oxidative enzymes used in metabolism -no fiber hypertrophy

Summarize the main effects of resistance training on skeletal muscle.

-increase in muscle CSA due to hypertrophy -type IIb become type IIa -no conversion from type II to I -myonuclei added to maintain domain -increase in pennation angle

State how fiber type proportions (and capillary density and myoglobin concentration) change during endurance training; state whether these effects are different between sexes? Between humans vs mice/rats; state whether changes in fiber type proportions are the result of fiber necrosis and subsequent regeneration, or fiber type transformation from one type to another.

-looked at in women and men before and after endurance training -type IIb decreased type IIa increased -no change in type I -shift toward FOG -increase in capillary density around all fiber types -mice showed same response -myoglobn concentration increases, to hold more O2 -chronic stimulation of rat muscles for different number of days showed the more days stimulated meant more shift from IIb>IIa -if done long enough IIa>I but this doesn't occur under normal conditions fast twitch fibers progressively transform to become more like slow twitch oxidative fibers IIB>IIx>IIa>(I)

Predict the relative difference in shortening velocity between different fiber types based MHC isoform and the type of activity they power (e.g., postural versus jumping muscle)

-mostly SO muscle = slowest contraction -FOG muscles -medium -FG muscles- fastest contraction SO postural FG jumping

List the four characteristics that broadly distinguish fiber types.

1. shortening velocity 2. suseptibility to fatigue 3. source of ATP 4. myosin isoform

Explain the relative proportion of ATP that is produced by different metabolic pathways over time with different kinds of activity.

100m dash 1/2 is from phosphagens 1/2 anerobic glycolysis a tiny bit from aerobic 800m half and half anerobic and aerobic (using glucose and glycogen) marathon all aerobic, some from glucose, some from lipids fat stores the longer you exercise the more likely to use mostly or all aerobic metabolism

Define the EPOC and oxygen debt; list the processes that are occurring during the EPOC phase; describe and graphically represent the relationship between the relative intensity of muscle activity and the magnitude of the oxygen debt/EPOC phase.

excess post exercise oxygen consumption (EPOC) at the start of exercise oxygen is taken from body stores, as you keep going you take it up from the environment -keep panting after exercise to replenish stores in the beginning you get and O2 debt, in the end debt must be repaid =post exercise consumption (EPOC) the more strenuous the activity the larger the debt in some cases rate of O2 uptake never matches rate of O2 usage and you create debt thoughtout the exercise =longer pay back phase if theoretical O2 demand exceeds VO2 max then you create a debt throughout exercise -replenish creatin phosphate , glycogen and ATP stores -oxidize lactic acid to pyruvate -restore oxygen to myoglobin

K+ accumulation in the T-tubules i. state the effects of increasing ECF K+ on RMP. ii. state the effects of changing RMP on force output. iii. predict the effects of increasing ECF K+ on force output.

fatigue is related to K+ accumulation in t tubules -what is the fact of EC K+ on RMP -too much K+= K leakes into cell causing slight deploraizations -how does a change in resting potential change peak force -once you get to -60mV resting p force output plumets -opposite of expectation -complicated mechanism increase in K+ = decrease if force

State in words and/or graphically depict the features of fatigue (e.g,. decreased force, decreased shortening velocity, and slowed relaxation)

twitch force declines with fatigue or may not be able to produce tetanus for as long, have a slower twitch speed (shortening velocity), slowed relaxation

State how fiber type proportions change during resistance training.

type IIb decrease type IIa increases type I showed no change type IIb fibers appear to transform into IIa see an increase in FOG fibers seem to be the default fiber

What are the two major metabolic consequences of a lack of oxygen? o Describe the metabolic pathways that occur in the absence of oxygen, and specifically how this pathway (anaerobic fermentation/glycolysis) results in NAD regeneration and ATP production with no oxygen

under anoxic conditions NAD, FAD do not regenerate and lactic acid is produced Anaerobic Glycolysis 2 pyruvic acid> (lactate dehydrogenase)> 2 lactic acid in the process 2NAHD2>2NAD which can be reused -2 ATP are produced, works v quickly

Summarize the effects of aging on skeletal muscle form, function and physiology.

-experience sarcopenia -see disuse atrophy atrophy worse for type II fibers increase in connective tissue -decrease in total fiber numbers due to reduced number of motor neurons axon terminals and motor units increase type II decrease in type I -decrease in force output -decrease in Vmax due to shorter fibers and fewer sarcomeres -reduciton in range of motion due to decreased muscle fiber length :tendon length -twitch speed slows down due to longer contraction and 1/2 relaxation times

List the common experimental paradigms (human and animal) for studying disuse; describe the characteristic of 'disuse' that lead to the most pronounced changes in muscle (e.g., load-bearing versus contraction).

-experimental paradigms for studying detraining in humans -bed rest -space flight -unilateral lower limb suspension -limb immobilization -paralysis due to spinal cord injury animals -hindlimb suspension -limb immobilization -muscle denervation (mechanical or pharmaological) -Curare- Ach-R antagonist -inability to contract -tetradotoxin-blocks Vg-Na+ channels (no AP) -Botulinum toxin-prevent Ach release absence of load bearing (not just contraction) is most important -in humans atrophy shrinking fibers (lose myofibrils) is equal in both fiber types

Summarize the main effects of endurance training on skeletal muscle.

-no fiber hypertrophy or increase in CSA -fiber type transformaitons (shift towrd slower MHC isoforms) -increase in type IIa (FOG) and decrease in FG -interconversion of type IIb>IIa fibers -in humans no change in proportion of type 1 fibers -in rates increase type 1 if training occurred for long enough -increase in oxidative enzymes krebs cycle enzymes, enzymes for FA transport and oxidation

Electron Transport Chain (ETC) § what are the molecules that power the ETC and where do they come from? § for a single glucose molecule how much ATP is produced as a result of the ETC? § where does the ETC take place? § as a standalone process what is the functional (energetic) importance of ETC? (Be sure to state the two main purposes of this ETC.)strictly speaking, does it require oxygen?

-powered by molecules from the krebs cycle NADH, FADH2, also H+ from water and O2 which we breath in -26-28 atp produced per glucose -takes place across the inner mitochondrial membrane -produces bulk of the ATP -regenerates NAD and FAD+ -requires Oxygen

list the effects of disuse on the somatic motor neuron and neuromuscular junction

-retraction of the axon terminal -sprouting -spread of AChRs -reduced excitation

Describe the location, anatomy and function of a muscle spindle

-stretch receptors, parallel with muscle fibers -dozens -100s of them/muslce group -send info to CNS about muscle length and change in muscle length -encased in connective tissue -intrafusal fibers are their contractile fibers central portion is non contractile wrapped around dendrite endings of contractual neuron gamma motor neurons

Describe the general properties of ATP storage, transport and production in cells.

1. ATP is the only field source in muscles 2. cells do not sorry very much ATP (5mM) 3. ATP is only made in the cell where it is used no transport between cells The rate of work depends on how fast a cell can make ATP, ATP has to be regenerates as fast it is being used The breaking of high energy phosphate bonds releases energy throughout the cell energy from food used to add phosphates to ADP

What are the four ways of regulating the rate of a metabolic pathway (e.g., glycolysis, Krebs, etc...); provide 1-2 examples of each.

1. changing substrate concentrations 2. changing enzyme concentrations 3. covalent modification -phosphorylation*** and others 4. allosteric modulation, non covalent binding ligand >enzyme at non active site increasing or decreasing activity example of phosphorylation is in smooth muscles when Pi bind MHC allowing atp hydrolysis to occur all rate limiting enzymes of glycolysis can be modified via covalent modification or allosteric modification phosphofruktokinase inhibited allosterically by ATP, activated by ADP meaning glycolysis is unregulated when ATP levels are low

State and/or identify mechanisms known to contribute to muscle fatigue

1. increased K+ =decreased force 2. decreased calcium reputake with increased Pi, ADP, ROS and decreased ATP 3. Calcium sensitivity of myofibril proteins is decreased with increased Pi, decreased pH, and increased ROS 4. Calcium release is reduced, RyR are inhibited by increased Mg and decreased ATP 5. max calcium activated force is reduced by increased Pi 6. shortening velocity is reduced with increased ADP 7. voltage sensor activation is reduced with decreased AP amplitude and reduced by voltage sensor inactivation Mg is required to break Phoshate bond

List the 6 factors that lead to a change in force output in a whole muscle

1. muscle size (bigger>more force>most important factor) 2. motor unit recruitment 3. fiber types composing the muscle/motor unit 4. muscle length and stretch of elastic elements (length tension curve) 5. speed of contraction (force velocity curve) 6. muscle pennation angle

List the three factors that lead to a change in force output in a single muscle fiber.

1. sarcomere length 2. fiber diameter 3. stimulation frequency

State and describe the elements of every skeletal muscle reflex.

1. sensory receptors=proprioceptors -muscle spindles, golgi tendon organs, joint receptors 2. CNS intergrates signal -excitatory and inhibitory interneurons 3. somatic neurons carry the output signal -alpha motor neurons 4. targe (effector) tissue are contractile skeletal muscle fibers -extrafusal muscle fibers

Describe the role and/or relative importance of each of the following in contributing to muscle fatigue. You should be able to provide actual evidence (data) suggesting whether these do or do not play an important role in muscle fatigue a. pH

Acidosis hypothesis due to lactate -not all fatigued muscles have a low pH -poor correlation between ph and contractile function -not a strong correlation between lactate and pH -sometime lactate is proceed during aerobic metabolism lactate does cause delayed onset muscle soreness NOT the primary cause of fatigue

Describe the main effects of disuse/detraining on skeletal muscle. a. define muscle atrophy; state whether atrophy is the result of fiber shrinking, fiber necrosis or both; state which muscle groups experience the most atrophy during disuse (i.e., postural); compare the relative decrease in fiber size of the different fiber types during atrophy in humans vs rats.

Atrophy- is the shrinking of fibers (loss of myofibrils) -type 1 and 2 atrophy relatively equally in humans during disuse - in rats saw decline in type 1 and an increase in type 2 cause by type 1 switching to type 2 fibers why- because slow twitch muscle are postural, most of their use comes from load bearing of the body against gravity -during disuse you also get an increase in connective tissue

List the dominant fiber types, using ANY of the appropriate terminology for their names.

Fast Glycolytic (FG) Type IIb (IIX) fast twitch white muscle Fast oxidative glycolytic (FOG) or fast oxidative (FO) Type IIa Slow Oxidative (SO) type I slow twitch red muscle

Provide a detailed description of the cellular level regulation of muscle size (balance between atrophy and hypertrophy); this description should include all relevant hormones, growth factors, autocrine/paracrine signals, receptors, etc...

Hormones required for normal muscle growth (during childhood and puberty) -GH -insulin -TH (premissive for GH) -testosterone Growth factors that regulate changes un muscle size (in developing and adult muscles) -insulin like growth factor (IGF-1l produced by the liver in response to GH) -Myostatin- a member of the TGF-b super family P13k-akt1 pathway mechanical factors that regulate changes in muscle size (in developing and adult muscles) -stretch (immobilization in a stretched position leads to new sarcomeres, intermittent stretch as in forceful isometric contraction leads to new myofibrils) -load bearing -tension/stimulation (use/disuse/contraction)

Define, properly apply and graphically visualize the terms: isometric,isotonic, concentric and eccentric contraction.

Isotonic contraction- force output with muscle shortening concentric= shortening F output eccentric= force output with lengthening Isometric contraction=force output with no muscle shortening -something is too heavy -sarcomere shorten -tendons stretch and ends of tendons do not move

Describe 1) the action potential response of the sensory neuron and 2) the outcome (to the extra- and intrafusal fibers) of the stretch reflex pathway during rest, stretch and contraction; In general, students should be able to explain and draw exactly what is happening between the muscle spindle and the muscle fibers (extra- and intrafusal) as a result of muscle spindle sensation during rest, stretch and contraction

Muscle spindles can respond to stretch can trigger a stretch reflex prevents damage due to overstretching -the addition of a load stretches the muscle and the spindles creating a reflex contraction 1. load added to muscle 2. muscle and muscle spindles stretch as arm extends 3. reflex contraction initiated by muscle spindles restores arm position

List and describe the different ways of identifying fibers types in a muscle (e.g., SDH, myosin ATPase, PCR to identify the MHC isoform)

Myosin ATP ase (basic solution)- dark type 2 light type 1 Myosin ATPase (acidic solution) -light type 2, dark type 1 SDH stains mitochondria so will be darker in SO fibers you can use PCR to separate can be used to separate different MHC isoforms because they are encoded by different genes -the relative thickness of each line correlates to the degree that MHC isoform is being expressed

state what myostatin is; define the role of myostatin in the regulation of muscle size; describe the effects of being a myostatin knockout; provide examples of systems in which we have investigated or learned about mysotatin via knockouts.

P13K-AKt1 -regulates balance between muscle synthesis and degradation IGF1/insulin>triggers production of P13K> phosphorylates Akt1 activating it > goes on to promote muscle growth -signaling pathways, increase protein synthesis -inhibits regulator myostatin pathways myostatin knockout mice show giant muscles deficiency in myostatin lead to overdeveloped muscles myostatin causes normal atrophy during disuse, if there is not atrophy muscles just keep growing

State the effect of pennation angle on force output and shortening velocity of a muscle, and explain why this relationship exists (a complete explanation of this effect will include proper knowledge of the terms ACSA and PCSA).

Pennation angle is the angle fibers come off a tendon at an angle the force produced by each fiber decreases, however you are about to fit more fibers into the same amount of space meaning force is effectively increased PCSA- physiological cross sectional area is always 90 degrees to fibers Acsa-Anatomical cross sectional area - cross section of muscle in a parrelel msucle pcsa and acsa are equal in a pennate muscle pcsa is increased a lot Force on a tendon= force cell* number of cells* cos theta theta is the angle between the tendon and the penated fibers pennate fibers are also shorter so they have decreased shortening velocities than parallel fibers

susceptibility to fatigue -State the factors that influence how likely a fiber is to fatigue. -Describe how a fiber could change (anatomically or biochemically to decrease susceptibility to fatigue.

SO fibers are least susceptible FOG are medium FG are most susceptible fatigue resisitance is influenced by their primary metabolic strategy (source of ATP) oxidative - steady tate metabolic process nothing builds up FG- produce lactate > problems anaerobic metabolism

Explain the relationship between fiber types and the muscle activity that they power (e.g, high jump vs jogging); be able to identify what fiber type would power different kinds of activity; discuss the relative contribution of genetics versus plasticity to fiber type composition in different kinds of athletes (e.g., sprinter versus weight lifter).

SO= long distance FOG= middle distance FG= sprint genetics is the primary factor, can be changed a little with plasticity

Provide evidence to support or refute the following statement: "an increase in muscle mass during resistance training is due to hypertrophy, not hyperplasia"

Study on body builders vs intermediate body builders vs normal people showed much larger bicep area but showed relatively similar #'s of muscle fibers, but much larger individual fibers

ATP synthase § what is the functional role of the ATP synthase molecule? § where is it found?

The ATP synthase is at the end of the electron transport chain, in the inner mitochondrial membrane it also H+ to pass out of the inner membrane to cytosol harnessing that energy to turn ADP into ATP

List the two (three really) main sinks of ATP in a muscle cell, and the three main sources of ATP in a cell; describe what the initial fuel sources are for each of these source pathways and state where they come from.

Three main sources 1. creatine phosphate 2. glycolysis 3. oxidative phosphorylation Sinks 1. Myosin ATP ase 2. SR calcium pump -also Na/K atp ase) Glucose from liver>glycogen>glycolysis>ATP or >oxidative phosphorylation > ATP glycolysis produces lactic acid Fatty acids/proteins+ oxygen>oxidative phosphorylation>ATP creatine phosphate gives on P to ADP> creatine and ATP

List the steps of embryonic muscle development; state the names of the transcription/regulatory factors involved in muscle cell development, as well as connective tissue development; describe how the steps of myogenesis differ (or are the same) between skeletal, cardiac and smooth muscle.

an embryo has three specific layers 1. ectoderm>nervous, epidermis 2. mesoderm> connective tissue and muscles 3. endoderm> epithelial glands myogenesis 1. embryonic mesoderm cells called myoblasts undergo cell division and enlarge 2. several myoblsats fuse together to from a myotybe 3. myotube matures into skeletal fiber myoblasts: have actin and MHC, no sarcomeres, no t tubules. when the align and fuse they become myotubes myotubes- immature multinucleated muscle fibers. Thick and thin elements. Some ACH receptors, some sarcomere organization myotubes then mature and organize to become mature muscle fibers skeletal go all the way, smooth and cardiac muscle cells stop developing at myoblast state Mesoderm>(Myo D, Myogenin, Myf)> myoblasts >(FGF>causes myoblast proliferation)>when FGF goes away cells align> ACh or prostaglandin trigger myoblasts to fuse into myotube>muscle fiber> muscle assembly connective tissue > (FGF)> fibroblasts> collagen > muscle assembly Myoblasts>motility and exploration> alignment>protein syntehsis>gap junciton formation (Sm and C stop here!) >depolarization with ACh and prostaglandin > calcium entry> membrane break down> myoblast fusion> myotube> formation in myofilaments, t tubules, basement membrane...

Characterize the inherent differences in fiber type composition between athletes that are trained for endurance vs resistance training; state the relative importance of genetics versus muscle plasticity in determining the fiber type composition.

athletes trained for resistance will have mostly fast twitch fibers and this trained for endurance will have mostly slow twitch fibers -mostly due to genetics and not muscle plasticity training

State why larger fiber diameter leads to increased force output

bigger cross sectional area> more force more contractile machinery/myofilamnets making fibers bigger= hypertrophy myofibrils enlarge then split creating more of them -downside to really big muscle fibers is myofibrils have less access to mitochondria

Differentiate between central and peripheral fatigue, and provide a list of proposed mechanisms that may underlie each condition.

central fatigue=psychological effects, protective reflexes peripheral fatigue= decreased NT's decreased receptor activation 1. acidosis -lactate -low ph may inhibit ca repute/release 2. metabolic fatigue -accumulation of metabolites/depletion of substrates 3. SERCA reduction -reduction in SERCA release and myofibrils sensitivity may reduce cross bridge activation slows> slows relaxation 4. Inexcitability/conduction failure- K+ accumulation in T tubules depolarizes sarcolema leading to Na channel inactivation and failure to conduct AP 5. Ischemia -msucle becomes ischemic during high intensity exercise

Reiterate and explain all of the information in the Table on Slide 14.

compares and contrasts properties of different fiber types -#mitochondria>fatiguability -Myosin ATP ase rate>fatiguability SR volume> calcium re uptake rate> duration of twitch and speed of shortening MHC isoform> Myosin ATPase rate >speed of shortening

state the effects of disuse on connective tissue; explain the (inverse) relationship between muscle fiber size and connective tissue volume.

connective tissue increases with disuse. connective tissue grows to fill space

ATP depletion i. does ATP depletion inhibit SERCAs and calcium reuptake?

during activity ATP levels are relatively constant larger decrease for type II than type I max force production does not occur until ATP falls below 20uM which is never found in a functioning cell calcium sensitvity is not disrupted by decreased ATP it has been shown that decreased ATP inhibits SERCA but its not significant in the context of muscle fatigue - relaxation rates slow -calcium levels stay high for a longer period of time -however adding ATP does no return muscle to normal relaxation rates =ATP is not the problem -something else must be inhibiting sercas which is causing slower reuptake inorganic phosphate levels influence force and lead to fatigue -force decreases as Pi increases -force is lower at all Pi concentrations at lower pHs -when Pi is present you need more calcium to produce the same force -Pi reduce calcium sensitivity of troponin molecules =decreased CB cycling increased inorganic phosphate does play a role in muscle fatigue

Give evidence of (or interpret novel data that is evidence of) central fatigue

example from class was people worked till exhaustion with eyes closed but could work harder again once they opened their eyes

Define muscle fatigue

fatigue= any decline in muscle performance that is associated with previous muscle activity reversible condition in which muscle is no longer able to generate or sustain power output as a result of previous activity

Describe and graphically visualize the 'length-tension relationship' at the level of the single muscle fiber AND at the level of the whole muscle; explain why this relationship exists.

force production by a muscle fiber depends on the sarcomere length at the initiation of contraction greatly shorted- decreased tension resting length - max tension produced excessive stretched -decreased tension produced optimal sarcomere operating length 80%-120% of resting length starting too contracted, proteins jam into each other staring to stretched less cross bridge cycling, less available myosin heads

Have a working knowledge of the standard, commonly used experimental models and independent variables for studying muscle fatigue (e.g., mechanically skinned fibers, glycerinated fibers, max twitch force, max tetanic force, half time to relaxation, half time to max force, etc.)

glycerinated= poke holes in the sarcolema =swiss cheese, everything from the outside gets in mechanically skinned= physical removal of sarcolema

Compare and contrast aerobic catabolism, anaerobic glycolysis and phosphagen use (based on the information in the slide labeled "ATP sources").

immediate ATP- phosphagens (CP,AP, adenylatekinase) v fast short term- aerobic glycolysis (anaerobic fermentation)-fast long term- oxidative metabolism -aerobic glycolysis/b oxidation, krebs, ETC, ox phosphorylation

Explain - with an accurate description of the relevant anatomy/structures - how force is produced during an isometric contraction without any total muscle shortening.

in an isometric contraction the sarcomere shortens but total muscle length does not change. This is possible because the elastic elements stretch. there is still force being produced, tension is developing as the tendons pull on the bone which is attached to the object its just not enough force to cause movement isometric contraction pulls on elastic elements allowing sarcomere to shorten -titin -epi, peri, endomysium (CT layers) collagen and elastic elements provide elasticity

state the changes in fiber type composition that occur during disuse.

in rats decrease in type one and increase in type two switching from type 1 to type 2

State how resistance training alters the pennation angle.

increase in angle of pentagon leads to increased force pennation angle changes during during training. it gets larger to produce more force

Describe the possible fates of lactate; explain the Cori cycle (include identification of important membrane transport proteins), and explain why humans don't just pee out excess lactate during anaerobic exercise

lactate still has stored energy so it is better to save it -can be converted back to pyruvate and used in the krebs cycle when O2 become available -glyconeogenesis via the cori cycle lactate is transported to the liver>pyruvate>glucose> back to muscle MCT's monocarboxylate transporters transport lactate across plasma membranes

Describe the location, anatomy and function of a joint receptor.

located in synovial joints moniter stretch of articular capsule prevent damage during flexion and extension proved info on join position and movement

State and draw the neuronal pathway of a golgi tendon's relaxation reflex pathway; describe the function of the relaxation reflex

muscel contraction stretches the golgi tendon if excessive load is placed on the muscle the golgi tendon reflex causes relaxation thus protecting muscle

describe the effects of disuse on fatigability; be able to draw this pattern graphically, or interpret novel data that might be showing this phenomenon; state the proposed mechanism by which increased fatiguability occurs during disuse

muscle fatigue more quickly after disuse proposed mechanism by which fatiguability occurs during disuse is decreased motor unit recruitment

Provide evidence (data) for or against the following statement: "Each individual muscle fiber in a muscle group is composed of only a single MHC isoform."

muscle fibers in reality have multiple MHC isoforms, mixture of fiber types Fiber types are a useful simplification rather than absolute categories PCR showed samples of single fibers that expressed multiple MHC isoforms

Explain the consequences of increasing the stimulation frequency of the somatic motor neuron (or an experimental stimulation electrode) on force output in a single fiber (e.g., the process of summation, treppe and tetanus). Be able to describe theses processes in detail, graphically display these phenomenon, explain the underlying physiological mechanism, and predict what this phenomenon looks like when scaled up to the level of the whole muscle.

muscle relaxes completely between single twitches summation- stimuli closer together do not allow for full relaxation summation leading to unfused tetanus- stimuli are far enough apart to allow slight relaxation but tension increases with each stimuli -summation leading to complete tetanus- muscle reaches steady tension, if muscle fatigues tension decreases rapidly more and more calcium becomes available to cells (reputake doesn't finish) additional force from passive tension of elastic elements tetanis> smooth contractions prevents sporadic movement, asynchronous fiber contraction prevents jerky movment part of the muscle always remains contracted Treppe- force of twitch increases even with complete relaxation -stair case effect -warmed up muscle> faster enzymatic activity -more CBC because MHC works faster -residual calcium

lactate accumulation i. differentiate between the role of pH and the role of lactate in muscle fatigue.

muscle with lactate had slightly slower relaxation rates, no change in force, some correlation between general acidosis and contraction

Describe the concept of muscle plasticity.

muscles can change with use and disuse

Define phosphagens and state their role in energy production in a muscle cell; state the dominant vertebrate and invertebrate phosphagens; provide a physiologically relevant range of concentrations for phosphagens in a muscle cell; describe the reaction facilitated by these molecules, being sure to identify the responsible enzyme; state the reaction facilitated by adenylate kinase, and describe its physiological importance

phosphates provide immediate ATP source without the need for O2 Creatine phosphate (vertebrates)or Arginine phosphate (invertebrates) + ADP> ATP with creatine kinase or arinine kinase creatine phosphate is found at about 15mM in skeletal muscle used to basically store ATP ADP+ADP > (adenylate kinase)> ATP+ AMP we don't store just ATP -need too much to store -too reactive -larger than creatine or arginine phosphate phosphagens used immediately for exercise type II fibers have higher concentrations of phosphagens make atp very quickly only 1 rxn required physiological imortance of adenylate kinase is that you are able to create ATP from existing molecules in the body

State the effects of resistance training on fiber size (CSA) and describe how these effects may (or may not) affect the various fiber types differently.

resistance training leads to a larger cross sectional area =more force production -mostly plays a role in type II type one do not work as well when they grow larger

Describe the basic characteristics and goals of resistance training; provide examples of activities that are considered resistance training; state the type of muscle contractions/activity that lead to increased muscle bulk.

resistance training works to increase force muscle can produce over a short period of time - weight lifting and shot put -strength training -lift heavier loads for short times -Resistance training> hypertrophy larger cells (fibers) -hyper place happens occasionally but is pretty rare -Type II fibers increase greatly in size 32% type 1 14% -type I don't increase that much because they're more effective when they're small

Describe in detail the process of muscle regeneration (following injury) by satellite cells; be able to state and recognize the transcription factors that are involved in this process

resting myofiber has myonuceli along edges and resting progenitor or satellite cells along its edges. trauma occurs -differentiation of satellite cells - move to injured fiber -fusion to damaged myofiber (>hypertrophy) -fusion of just cells together to produce new myofibers (hyperplasia) -regenerate myofiber with central nuclei -nuceli move back to edges of the cell Pax 7 myo C myogenin Myf 5 MyHC

Verbally explain or draw a diagram to describe the proposed mechanism for muscle memory; define with words and a corresponding picture the concept of the myonuclear domain; state the location and role of satellite cells.

satelitce cells fuse with myofibril adding nuclei to myofibril -help with hypertrophy -myonucelar domain =amt of fiber that nuclei controls or maintains -hypertrophy without more nuclei leads to an increase in the myonucelar domain -can be a problem if nuclei can't handle that much cell -adding nuclei conserves myonucelar domain -when muscle atrophy (shrinks) the number of nuclei does not decline -next training cycle nuclei are already present and it happens more quickly -nuceli are not lost during atrophy -nuclei drive myofibril addition

Define shortening velocity, state the factors that will effect the shortening velocity, and verbally and graphically explain the nature of the relationship between shortening velocity and force output (e.g., the force-velocity curve); be able to explain the underlying reason why the force velocity relationships exists.

shortening velocity= speed at which a muscle changes length during contraction -shortening velocity is dictated by the MHC isoform -for a single MHC isoform (in a single fiber) shortening velocity under a given load is directly proportional to the number of sarcomeres in series -so for muscles of the same length the one with more sarcomeres (longer fibers) will shorten at a higher velocity -the shortening velocity of a muscle declines with increasing force it takes time for myosin to bind all the actin as shortening velocity decreases amount of CBC taking place decreases and force output also decreases or you could think, it takes longer to produce more force cause you gotta wait for all the myosin heads to bind the actin to produce sufficient force Power-F*V and is maximized at a glance between F and V, about 1/3 of V max

frequency of contraction - differentiate between twitch duration, shortening velocity, relaxation rate and frequency of twitch (listed as frequency of contraction on the slide) - State the factors that can increase/decrease the frequency of twitches; be sure to understand those things that will increase the shortening velocity vs those things that will increase the relaxation rate. (Technically both of these are necessary to speed up the overall twitch duration, but we often think of needing to specifically increase relaxation rates/calcium reuptake to increase the frequency of twitches). - Draw or interpret a graph of force or [Ca2+] across a twitch between different fiber types and superfast sonic muscles.

twitch duration is dependent of speed of calcium repute by the SR type II fast twitch fibers remove calcium from cytosol more quickly -change SERCA isoforms and number of SERCA -pumps calcium back in faster -parvalbumin is likely more common in fast twitch helps pump calcium back into the SR by binding it in the cytosol