BMS150 Week 9 Skeletal Muscle Physiology II PDF

Physiology 4.02 Skeletal Muscle Physiology II Dr. Hurnik BMS 150 Week 9 Outline Muscle contraction Cross-bridge cycling Whole muscle contraction Isometric contraction Isotonic contraction Muscle relaxation Skeletal Muscles in action Fiber types Energy systems Phosphagen Glycogen-lactic acid Aerobic...

Physiology 4.02 Skeletal Muscle Physiology II Dr. Hurnik BMS 150 Week 9 Outline Muscle contraction Cross-bridge cycling Whole muscle contraction Isometric contraction Isotonic contraction Muscle relaxation Skeletal Muscles in action Fiber types Energy systems Phosphagen Glycogen-lactic acid Aerobic Recovery Muscle strength, muscle power, endurance Skeletal Muscle remodelling Growth Atrophy Learning Outcomes Describes the steps of the cross-bridge cycle, including: Role of: actin, myosin, tropomyosin, troponin, and ATP Describe the relationship between the sarcomere length and muscle tension Compare and contrast isotonic vs isometric muscle contractions Describe muscle relaxation, including: Role of: L-type Calcium channel, ryanodine receptor, movement of calcium Briefly describe the role of SERCA, sodium/calcium exchanger pumps, calsequestrin and calreticulum Compare and contrast type I and II muscle fibers (including type IIA and IIB), including their: Contraction time, innervation, resistance to fatigue, force production, myoglobin density, mitochondrial density, capillary density, oxidative capacity, glycolytic capacity, and major storage fuel. Learning Outcomes Describe the three energy systems used by skeletal muscle, including: Pathway, approximate duration, and activity types. Replenishment during skeletal muscle recovery Describe the factors that contribute to muscle strength, muscle power, and muscle endurance Define muscle hypertrophy, hyperplasia, and lengthening and stimuli for each. Define muscle atrophy (acute and chronic), and list common causes. EC coupling – cross-bridge cycle In the muscle fiber cytosol, Calcium binds to troponin C § When calcium binds to Troponin C, The troponin complex undergoes a conformational change and Troponin T “pulls” tropomyosin and Troponin I off of the myosin-binding site of G-actin subunits § Myosin is now able to bind to G-actin and form a cross bridge Let’s take a look at the steps of the cross-bridge cycle to initiate muscle contraction. Cross-bridge cycle - 1 1. ATP hydrolysis When ATP is bound to myosin, its like “eyeing” the actin, but not yet highly in love with it When it hydrolyzes the ATP into ADP & Pi, now there is a higher affinity for actin —> myosin pivots § Prior to Myosin being able to bind to actin, it must be “energized”: When Myosin is bound to ATP, it lowers it’s affinity for actin and there is no cross-bridge formation. Intrinsic ATPase activity in the myosin head then hydrolyses ATP à ADP + Pi § (both remain bound to the myosin head) Hydrolysis causes the myosin head to pivot, moving down the actin filament so that it lines up with a new actin monomer. Anatomy and Physiology (Betts et al). Figure 10.11 Cross-bridge cycle - 2 2. Cross-bridge formation § Calcium binding to troponin, has uncovered myosin- Cross-bridge binding site on actin § The energized myosin head attached to the myosinbinding site on actin & Pi is released § Creates a myosin-actin cross * bridge = Cross-bridge Anatomy and Physiology (Betts et al). Figure 10.11 Cross-bridge cycle - 3 3. Power stroke § The cross bridge generates force as myosin neck rotates toward center or sarcomere Actin and myosin filaments slide post one another Z lines get closer together, shortening the sarcomere & generating force Anatomy and Physiology (Betts et al). Figure 10.11 § ADP dissociates from myosin and the actin-myosin complex is left in a rigid, “attached” state Have to let go of the ADP Anatomy and Physiology (Betts et al). Figure 10.10 Cross-bridge cycle - 4 4. Detachment of myosin from actin § ATP binds to myosin and it detaches from actin § What happens if there is no more ATP available? Muscle rigidity Thinking question: Review – Why does binding of ATP case myosin head to detach from actin? When ATP is bound to myosin, affinity for actin is significantly diminished —> myosin not interested as much in the actin vs ATP Irreversible actin-myosin cross bridges are stuck —> muscle rigidity Ca++ leaking out of things when death occurs § Several hours after death, all the muscles of body go into contracture (rigor mortis), why does the rigidity occur? Anatomy and Physiology (Betts et al). Figure 10.11 Cross-bridge cycle – big picture Review: Describe the steps of each stage in 1-2 bullet points. Anatomy and Physiology (Betts et al). Figure 10.11 Sarcomere length The amount of actin and myosin filament overlap determines the tension that is developed by a contracting muscle. mosicin a B. With further shortening, full tension is maintained. A B. Any additional shortening of sarcomere length results in decreased tension C. Actin filament has already overlapped all cross-bridges of the myosin filament, but has not yet reached the center of the myosin filament. mu D. No actin-myosin overlap, thus no tension developes Guyton and Hall Textbook of Medical Physiology (Hall). 13th ed. Figure 6-9, page 81 Whole muscle contraction Isometric vs isotonic contractions § Isometric contractions: Muscle contracts against force transducer without decreasing muscle length Occurs when the load is greater than the force of muscle contraction § The muscle creates tension when it contracts, but the overall length of the muscle does not change Guyton and Hall Textbook of Medical Physiology (Hall). 13th ed. Figure 6-12, page 83 Whole muscle contraction Isometric vs isotonic contractions § Isotonic contractions: Muscle shortens against a fixed load Occurs when the force of the muscle contraction is greater than the load and the tension on the muscle remains constant When the muscle contracts, it shortens and moves the load Likely more muscle fibres that were recruited, more sarcomeres overall that were shortened, causing a lot more force & tension to be generated, which is greater than the load Guyton and Hall Textbook of Medical Physiology (Hall). 13th ed. Figure 6-12, page 83 Muscle relaxation When the sarcolemma is no longer depolarized, the L-type calcium channels no longer trigger release of calcium from the SR through the ryanodine receptor § L-type channels return to their resting membrane potential state Calcium is then re-sequestered into the SR § SERCA pumps calcium into the SR § Sodium/calcium exchanger pumps calcium into the ECF Minor in skeletal muscle § Calsequestrin and calreticulin bind the free calcium within the SR Medical Physiology (Boron and Boulpaepl). 3rd ed. Figure 9-8. Skeletal muscles in action – fiber types There are two main types of muscle fiber types: § Type I – aka Slow fibers Used to hold onto oxygen by muscles Generally smaller and innervated by smaller nerve fibers More capillaries to supply higher amounts of oxygen Lots of mitochondria to support high levels of oxidative metabolism Depends a lot on oxygen —> slower fibres take longer to be activated Lots of myoglobin, giving a reddish appearance § Type II – aka Fast fibers Larger in size and innervated by large nerve fibers Makes them faster Lots of SR for rapid Ca2+ release Lots of glycolytic enzymes present Energy can be derived from oxidative metabolism and anerobic metabolism, based on subtypes § Type IIA – Fast oxidative glycolytic fibers § Type IIB – Fast glycolytic fibers Anaerobic Fiber Type Slow Twitch Fast Twitch A Fast Twitch B Slow Faster fastest Size of Motor Neuron Small (fiber diameter) Bigger Really big Contraction Time Title Note Resistance to fatigue Very resistant Fatigue quickly (no mitochondria) Activity used for Low-force, endurance (i.e. postural muscles) High-force, quick fatigue (i.e. jumping) Force Production Slow, lower magnitude Quick, higher tension Mitochondrial density High Some none Capillary Density High Medium Low Oxidative capacity High Low none Glycolytic capacity Minimal Medium High Major Storage Fuel Fat Glycogen glycogen Lots of blood supply, mitochondria Fast vs Slow twitch muscle fibers Athletic training has been shown to change the relative proportions of type I and type II muscle fibres very little. § However, you can change the size of different individual muscle fibres with particular types of training § Proportions of type I and II fibers seems to be partially determined by genetic inheritance, which in turn may help determine what are of athletics is best suited to each person FYI - Recorded percentages of slow-twich (I) vs fast-twitch (II) fibers in quadricep muscles of different types of athletes Athlete I II Marathoners 18 82 Swimmers 26 74 Average male 55 45 Weight lifters 55 45 Sprinters 63 37 Skeletal Muscle Energy There are 3 different metabolic systems responsible for recycling AMP and ADP back into ATP to provide a continuous supply of ATP in muscle fibers Review – how was ATP involved in cross-bridge formation? § 1. Phosphagen system § 2. Glycogen Lactic acid system § 3. Aerobic system Skeletal Muscle Energy - Phosphocreatine Phosphorylated creatine molecule has a high energy phosphate bond § High energy phosphate bond of phosphocreatine has more energy than the bond of ATP § Serves as a rapidly mobilizable reserve of high energy phosphates in skeletal muscle and brain - - * Enzyme name FYI A Anatomy and Physiology (Betts et al). Figure 10.12 Skeletal Muscle Energy – 1. Phosphagen system Both phosphocreatine and ATP together constitute the phosphagen system § These compounds maintain a reserve of high energy phosphates that can be used as needed § Provide 8 to 10 seconds of maximal power eg. 100m max sprint running § Afterwards, gone until it’s replenished Skeletal Muscle Energy – Glycogen After absorption into a cell, glucose can be broken down immediately via glycolysis into energy for the cell § Can also be stored in the form of glycogen All cells are capable of storing some glycogen, certain cells can store large amounts: § Hepatocytes: 5-8% of their weight as glycogen § Muscle cells: 1 to 3% of their weight as glycogen on average Varies depending on the type of fiber! Skeletal Muscle Energy – 2. GlycogenLactic Acid system Glycogen-lactic acid system § Initial stage of this process is glycolysis Pyruvate —> lactic acid Pyruvate Glucose ________ is split into two ________ molecules, 2 generating a net _____ ATP. Pyruvate —> acetylCoA —> CAC —> NADH, FADH2 —> ETC - mitochondria!! Lots of ATP Review: generated § If there is sufficient oxygen, what happens next? § If there is insufficient oxygen, what happens next? What happens in the case of Type IIB fibers, when there are minimal mitochondria? Lactic acid Anatomy and Physiology (Betts et al). Figure 10.12 Skeletal Muscle Energy – 2. GlycogenLactic Acid system In the case of insufficient oxygen § Pyruvate will be converted into _____ Lactic acid (catalyze by Lactate________), dehydrogenase which diffuses out of the muscle cells into the interstitial fluid and blood What else is generated in this reaction, what is it’s purpose? Generate NAD+ (feeds back into glycolysis) Glycogen-lactic acid system can sustain maximal muscle contraction for 1.3-1.6 minutes. Skeletal Muscle Energy – Cori Cycle Substrates – Lactate – Cori Cycle Liver Muscle Questions: 4 ATP per Glucose Glucose Glycolysis Gluconeogenesis 2 NADH 2 NAD+ 6 ATP Blood 2 ATP 2 pyruvate 2 NADH Glucose 2 pyruvate LDH 2 lactate 2 NAD+ LDH 2 lactate 2 lactate What is the cycle OVERALL net loss or gain of ATP in the Cori cycle? What is the purpose of the Cori cycle? Repurpose lactate to turn back into glucose Helps to move the lactate away from the muscle, make sure we do not accumulate lactic acid Regenerate NAD+ Skeletal Muscle Energy – 3. Aerobic system In presence of oxygen, pyruvate is broken down into carbon dioxide, water and energy via citric acid cycle and ETC § As long as nutrients in the body last, the aerobic system can be used for unlimited duration § Eg. Used in sports that require extensive expenditure of energy: Marathon, cross-country skiing § Athletic events over 4 – 5 hours deplete glycogen stores of the muscle and depend on energy from other sources (mainly fats) Skeletal Muscle Energy - Summary 3 different muscle metabolic systems to supply the various degrees of energy that are required for various activities Muscle Metabolic Energy Duration of Maximal Systems Muscle Acitivty Activity Types Phosphagen System 8-10 seconds Power Surges Glycogen-Lactic acid system 60-90 seconds Intermediate athletic activities Aerobic System “Unlimited” Prolonged athletic activities Can be constant shifting (especially during some sports - eg soccer game) between extreme spurts, intermediate power and endurance Skeletal Muscle Recovery Energy systems must be replenished § Phosphocreatine can be used to replenishes levels of ATP § Glycogen-lactic acid system replenishes both phosphocreatine and ATP § Oxidative metabolism can replenish all systems: ATP, phosphocreatine and glycogen-lactic acid system Additional oxygen is needed – “oxygen debt” Glycogen levels must be replenished Skeletal Muscle Recovery – Oxygen debt After exercise is over, stored oxygen must be replenished by breathing extra amounts of oxygen above normal requirements § In heavy exercise all stored oxygen is used within ~1 minute of aerobic metabolism Also need 9 more liters of oxygen to provide for reconstituting the phosphagen system and the lactic acid system Total oxygen that must be “repaid” = 11.5 liters Oxygen being stored: dissolved in blood, bound to hemoglobin,bound to myoglobin in the muscle Skeletal Muscles in action - Muscle strength Muscle strength is determined mainly by its overall size § Maximum contractile force is between 3 and 4kg/cm2 of muscle cross-sectional area § Eg. Weight lifter with quadriceps muscle with a crosssectional area up to 150 square centimeters translates into a maximal contractile strength of 525 kg all applied to the patellar tendon Easy to see how this tendon can rupture or avulse Skeletal Muscles in action - Muscle Power Measure of the amount of work that the muscle can perform in a given period of time § Determined not only by strength of the muscle contraction but also by its distance and rate of contraction § FYI – measured in kilogram meters/minute (kg-m/min) Eg. Eg. A muscle that can lift a kilogram weight to a height of 1 meter or that can pull some object horizontally against a force of 1 kg for a distance of a meter in 1 minute is said to have a power of 1 kg-m/minute Skeletal Muscles in action - Muscle Power FYI - Max Power of highly trained athlete using a wide range of muscles: TIME Kg-m/min First 8 to 10 seconds 7000 Next minute 4000 Next 30 minutes 1700 Person has capability for extreme power surge for short period of time § For long term endurance events the power output of the muscles is only ¼ as great as during initial power surge Skeletal Muscles in action - Muscle Endurance Depends on nutritive support for the muscle Amount of glycogen that has been stored in the muscle prior to the period of exercise § High CHO diet stores more glycogen in muscles than mixed diet or high fat diet Also greatly depends on the type & size of muscle fibre that is predominant in the muscle under investigation Skeletal Muscle – effects of training Principals of muscle development: § Muscles that function under no load, even if they are exercised for hours on end, increase little in strength § Muscles that contract at more than 50% maximal force of contraction will develop strength rapidly even if contractions are performed only a few times each day § Experiments on muscle building show that 6 nearly maximal muscle contractions performed in 3 sets 3 days a week give approximately optimal increase in muscle strength, without producing chronic muscle fatigue Skeletal Muscle Remodeling - Growth Muscle Hypertrophy § Results from an increase in the number of actin and myosin filaments in each muscle fiber = enlarges individual muscle fibers § Enzyme systems providing energy also increase, especially those for glycolysis. § Occurs to a much greater extent when muscle is loaded during contractile process Under rare conditions of extreme muscle force generation, the actual number of muscle fibers increases. § Occurs due to linear splitting of previously enlarged fibers. § What do you suppose this is called? Hyperplasia Skeletal Muscle Remodeling - Growth Muscle lengthening § Occurs when muscles are stretched to a greater than normal length § Causes new sarcomeres to be added at the ends of the muscle fibers where they attach to the tendons When a muscle continually remains shortened to less than its normal length, sarcomeres at the ends of the muscle fibers can disappear Lack of stretching Wearing high heel shoes habitually, shorten Achilles tendon Skeletal muscle remodeling - Growth Summary Muscle Remodeling - growth Hypertrophy (common, weeks) – Caused by near maximal force development (eg. weight lifting) – Increase in actin and myosin – Myofibrils split hypertrophy Hyperplasia (rare) – Formation of new muscle fibers – Can occur with endurance training Hypertrophy and hyperplasia – Increased force generation – No change in shortening capacity or velocity of contraction lengthening hyperplasia Lengthening (normal) – – – – Occurs with normal growth No change in force development Increased shortening capacity Increased contraction velocity Skeletal muscle remodeling - Atrophy Muscle Atrophy Losing the actin & myosin filaments § Muscle no longer receives contractile signals required to maintain normal muscle size § Causes of muscle atrophy Denervation/neuropathy Tenotomy Loss of tendon Sedentary lifestyle Plaster cast Space flight (micro-gravity) No load Skeletal Muscle Remodeling - Atrophy Muscle Rem Atrophy begins almost immediately § Acute/subacute Degeneration of contractile proteins Decrease max force of contraction Decrease velocity of contraction If contractile signals return, full return to function can occur in as little as 3 months § Eg. Nerve supply grows back, Ca atrophy weeks months/ years atrophy with fiber loss Skeletal muscle remodeling - Atrophy Muscle Rem Muscle disuse for years (Chronic) § Functional return of the muscle decreases, with no return of function after 1 to 2 year § In final stages, muscle fibers are destroyed. Number of sarcomeres/fibre will often be lost, resulting in a shortening of the muscle + fibrosis à contracture Fiber are replaced by fibrous and fatty tissue with little contractile proteins Ca atrophy weeks months/ years atrophy with fiber loss References Alberts et al. Molecular Biology of the Cell. Garland Science. Betts et al. Anatomy and Physiology (2ed). OpenStax Hall. Gyton and Hall Textbook of Medical Physiology (13th ed). Elsevier Boron and Boulpaep. Medical Physiology (3rd ed). Elsevier