Lecture Notes On Muscle Contraction PDF

Lecture 8 How does actin and myosin work together to produce skeletal muscle contraction? - Sliding filament theory What happens in the sliding filament theory to shorten muscle? - Muscle shortening occurs due to the movement of actin filaments over myosin filaments - Distance between Z...

Lecture 8 How does actin and myosin work together to produce skeletal muscle contraction? - Sliding filament theory What happens in the sliding filament theory to shorten muscle? - Muscle shortening occurs due to the movement of actin filaments over myosin filaments - Distance between Z discs decreases - Myosin doesn’t change (length of A band is maintained) - Actin slides inwards (H and I bands become narrower) What is a motor neuron? - Transmit electrical signals from spinal cord to muscle fibers Is myosin head binding synchronized during muscle contraction? - No actin will go back keeping it steady movement What did the electrically stimulating muscle fibers on frogs show? - When stretching fibers so none overlap has very lower force - When overlapping the actin, it is very relaxed creating little force - When myosin and actin overlap with intermediate force it generates force What is the optimal sarcomere length? - 2.0 - 2.5 μm - Where you generate all your force from What percentage of body weight is made up of skeletal muscle? - 40-50% Where is calcium stored in skeletal muscle? - Sarcoplasmic reticulum Which actin regulatory protein covers myosin binding sites? - Tropomyosin Lecture 9 What are the steps for contracting a muscle? - Singal from the brain travels down the spinal cord to the muscle fibers causing an action potential - Action potential travels to alpha motor neuron - Goes to terminals which trigger a release of ACh - ACh is released into the synaptic cleft which binds to nicotinic receptors - Once that is binded, it depolarizes at the end motor plate - Travels to the sarcolemma - Into t-tubules - Once it reaches t-tubules it triggers calcium from sarcoplasmic reticulum and binds to troponin - Tropomyosin reveals the binding site on the actin for the myosin to bind to - It's in a cocked position at a relaxed state - It binds to the actin, the ADP + Pi must be released in order to create the power stroke  - Once it is pulled in, the new ATP breaks off the bind and ATP is turned into ADP + Pi and the energy is used to cock back the myosin head (continues to interact as long as calcium is available) Lecture 10 Are all skeletal fibers created equal? - No How many different fiber types do humans have? - 3 What are the 3 types of fibers that a human has? - Slow fibers: type I - Fast fibers: type IIx and type IIa Are there different fibers within each muscle? - Yes, there isn’t just one type of muscle fiber within a given skeletal muscle - Also driven by genetics How can you tell each fiber apart? - How fast the contraction is - The force of the contraction - The fatigue resistance - Sarcoplasmic reticulum proteins, how fast calcium is being shot out - The amount of ATP being generated - The size of the fiber and how it is stimulated - How well the fiber utilizes fats, carbohydrates and proteins - How many types of enzymes that are associated with glycolysis and the Krebs cycle - Blood flow related properties, outside the muscle fiber - Capillary density around the fiber, if it needs a lot oxygen or not What is myoglobin? - binds oxygen, stored in muscle, links to oxygen dropped off by the capillaries, reserved oxygen stored in muscle fiber - Stores and carries oxygen What makes up a type I muscle fiber? (slow twitch) - High capillary density, using a lot of oxygen, are aerobic, using krebs cycle and ETC - High myoglobin concentration - High mitochondria (uses a lot of oxygen) - High resistance to fatigue - Uses ETC, mitochondria, and krebs cycle - Low contraction rate - High efficiency, uses little ATP but still efficient - Moderate force - Long periods of exercise with low energy - Ex: distance running, cross country skiers What makes up a type IIa muscle fiber? (fast twitch) - Intermediate fiber - Moderate capillary density - Moderate myoglobin concentrations - high/moderate mitochondria - high/moderate fatigue resistance - Both anaerobic and aerobic - High ATPase activity, breaks down ATP really fast - Intermediate contraction - Moderate efficiency - High force - Ex: cross-fit, soccer What makes up a type IIx muscle fiber? (fast twitch) - Low capillary density - Low myoglobin concentrations - Low mitochondria (glycolysis) - Low resistance to fatigue - Anaerobic energy source - Highest ATPase (breaking down a lot of ATP) - Highest contractions, really fast - Low efficiency - Highest force generation - Ex: divers, powerlifters Can fiber type be altered by endurance and resistance exercise training? - Yes but can only go from fast to slow twitch - Can’t go from slow to fast twitch How can a fiber change from fast to slow twitch muscle fiber type? - Mitochondrial biogenesis which is similar to converting fast twitch to slow twitch fibers - More capillaries since it needs more oxygen Can a fiber type go from a slow to a fast phenotype? - No What happened in the experiment with Buller and Eccels? - Did surgeries on cats - Surgically switched slow and fast twitch nerves - Turned slow to fast, and redid the same surgery to make sure it did actually work - Changed the alpha motor neuron signal - You can use surgically intervention to change slow to fast neurons How does resistance training increase strength if there is little evidence of slow to fast conversion? - Hypertrophy and changing in diameter What happens to muscle adaptations in resistance training? - There is a steep increase - Learn the techniques during the first couple of weeks - After the first couple of weeks it plateaus, and the growth is coming from hypertrophy What is hypertrophy? - Increase of muscle size - Laying down more actin and myosin What causes hypertrophy? - The signal is the muscle stretch or the force being generate by the fiber to overcome the resistance - Satellite cells that are housed within the fiber, are changed into nuclei to increase myonuclear domain - Insulin-growth factors (IGF) is the primary signaling pathway - ↑ IGF = hypertrophy What is the signal for IGF to be engaged in resistance? - The stretch against the force What happens to skeletal muscle when endurance and resistance training are done together? - TSC ½ increases from endurance training - And it blocks mTOR which is in resistance training - You won’t get as much hypertrophy since it is being blocked from endurance training What is hyperplasia? - The increase of muscle fibers Can hyperplasia be a result of exercise training? - Hyperplasia doesn’t occur with resistance training What causes hyperplasia to happen? - When satellite cells in skeletal muscle potentially form into new muscle cells - Myostatin is knocked out - Can’t split apart and make new cells - Myostatin isn’t restricted - Comes from a gene mutation What is myostatin? - Is a protein that restricts muscle growth - Less myostatin = more muscle growth Does myostatin regulate muscle growth? - Yes What happened in the case report with the baby with hyperplasia? - At birth the child had an increase of muscle size in the thighs and arms - The child had a decrease of myostatin gene expression - It can impact smooth muscle, cardiac muscle, and skeletal muscle  - Took MRI to compare muscle mass and saw an increase in the child - The bone size didn’t change - More muscle cells can form At birth in the case report, what happened to muscle size in the thighs and arms? - Increased Which best explains the results of the case report about the child with big muscles? - Decreased myostatin gene expression Lecture 11 What is the definition of VO2? - The volume of oxygen consumed by the body at any given point Why is oxygen important for exercise? - To generate ATP What is the Fick equation and what does it measure? - VO2 = CO x a-vO2 diff - Measures the volume of oxygen being consumed - CO is cardiac output (Q) - a is arterial - v is venous What is cardiac output? - The amount of blood leaving the heart in a minute Where are capillaries located? - They fall between the arterial and venous What is a-vO2 diff? - It measures the amount of oxygen extracted or utilized - The difference in oxygen content of blood between the arterial blood and the venous blood What happens to a-vO2 diff when going from rest to exercise? - Increases - More oxygen is being extracted from blood, to go into mitochondria to make more ATP - The body needs more oxygen when exercising, therefore it will extract more from the blood - Has a greater ATP demand when exercising How does chronic aerobic exercise training affect a-vO2 diff? - Rest - No change - Submaximal - No change - Maximal - Increase - Can contract more oxygen  - It takes the same amount of oxygen for a sedentary and trained person to do the same amount of exercise - A trained person go longer since they can contact more oxygen What happens to venous oxygen contact with aerobic exercise? - Decreases - There is less oxygen since there are more capillaries - The venous content stays the same as a sedentary person, they are just able to pull off more oxygen making the venous levels go down What happens to arterial oxygen contact with aerobic exercise? - No change - You can’t increase something that is already at 100% What changes occur to the skeletal muscle after chronic aerobic exercise training that would facilitate oxygen extraction? - Mitochondrial biogenesis (more mitochondria, utilize more oxygen) - Angiogenesis (amount of capillaries surrounding it) - Will work together to get more oxygen into that skeletal muscle What increases oxygen extraction? - Mitochondrial biogenesis - Angiogenesis What is angiogenesis? - Formation of new capillaries from existing capillaries What are the two types of angiogenesis? - Capillary intussusception - Sprouting angiogenesis What is intussusception angiogenesis? - Taking a preexisting capillary and making it into two by splitting down the middle creating a wall in between What is sprouting angiogenesis? - A bud growing from the side of the capillary forming into another capillary What is the exercise stimulus in angiogenesis? - The mechanical forces on preexisting capillaries from exercise, which is the signal - Shear forces (friction of RBC bumping into the walls of the capillaries) - Compression (surrounded by skeletal muscle fibers, when it contracts the blood vessel compresses on the muscle) - Stretch (force from the blood pressure increases) What is molecular signaling in angiogenesis? - Vascular endothelial growth factors (VEGF) being released into the cells, in the capillaries for angiogenesis to occur - Only occurs when muscle is contracting How does increasing capillary numbers facilitate the diffusion of oxygen from red blood cells to contracting skeletal muscle? - During exercise more capillaries open so there is more oxygen - Increase transit time - Decrease diffusion distance of oxygen to mitochondria since there are more capillaries - Better at making ATP, exercising longer How does resistance training impact angiogenesis? - Doesn’t increase - Not a stimulus strong enough to do, doesn’t reach threshold - Don’t see an increase because of skeletal hypertrophy, it is pushing the capillaries out of the slide How does resistance training impact mitochondrial biogenesis? - Expansion of density - It can accommodate more oxygen - Expand network for a trained person How does endurance training lead to a greater a-vO2 diff? - The greater capillary networks that surround that muscle fiber which allows blood to move slower for the diffusion to occur into that muscle fiber - A smaller distance for that blood to diffuse into the mitochondria - The mitochondria gets bigger so it can utilize the oxygen What type of exercise training has been associated with the greatest increases in capillary numbers? - Endurance exercise training Endurance exercise training results in what in the blood flow of capacity to contracting skeletal muscle? - Increase Lecture 12 What is the equation for cardiac output? - CO = HR x SV What is the resting cardiac output average? - 4.5 L/min for females - 5 L/min for males What happens to cardiac output when going from rest to exercise? - Increases - It increases to meet the oxygen demands - Blood leaving the left ventricle - More delivery oxygenated blood from heart to the working skeletal muscle Why do we need cardiac output to increase during exercise? - When exercising we need more ATP, to get more ATP we need more oxygen, to get more oxygen we need to extract more oxygen from the blood coming by muscle cell, in order  to get more oxygen to that muscle cell we need to deliver more, and that's where cardiac output comes into play - HR and SV must change during exercise, if it doesn’t then cardiac output doesn't change What happens to heart rate when going from rest to exercise? - Increases linearly with increasing exercise intensity - Needs to increase with intensity to meet the oxygen demand What is the average resting heart rate? - 60-70 bpm untrained What is the maximal heart rate? - 220 - age What causes the heart rate to increase? - Need to get more blood to the working skeletal muscle for more oxygen How does the heart rate increase? - The autonomic nervous system interacts with the SA node, releases ACh which is also released in synaptic cleft What happens to parasympathetic to increase heart rate? - The vagus nerve interacts with the SA node - The vagus nerve releases ACh which binds to muscarinic receptors in the heart to slow down heart rate - Causes the SA node to depolarize to resting heart rate - By slowing down this process it will increase heart rate What happens to sympathetic to increase heart rate? - Starts being used at 100 bpm - Driven by cardiac accelerator nerve that also interacts with SA node - By engaging sympathetic and cardiac accelerator to make heart rate higher than 100 bpm What is stroke volume? - The amount of blood ejected from the heart in one contraction What happens to stroke volume when going from rest to exercise? - Increases What is systole? - The contraction phase of the cardiac cycle What is diastole? - The relaxation phase of the cardiac cycle What happens to stroke volume when exercising on an untrained person? - Peaks and plateau at 40% of VO2 max - Everything passed 40% is driven by heart rate and not stroke volume - The time has shrunk and the timing of systole and diastole go down. Diastole is reduced, the time to fill up the heart with blood decreases - The VO2 max can’t increase the amount of blood being ejected since the heart rate is too fast What is the average stroke volume at rest? - Males: 70 ml per beat - Females: 60 ml per beat What is the average stroke volume when exercising? - Males: 110 ml per beat - Females: 90 ml per beat What variables contribute to increasing the stroke volume with exercise? - Preload - Contractility - Afterload What is working against stroke volume? - Blood pressure (afterload) What is preload? - The amount of blood in the ventricle prior to contraction - Filling the chamber with more blood to get more out What is contractility? - The strength of the ventricular contraction - Greater force of myosin and actin - With the same amount of blood within the heart, contracting more will increase the amount produced What is afterload? - Aortic blood pressure - The amount of pressure in your systemic circulation that your heart has to pump against to get blood out - Working against the valve - The blood vessels have a pressure head that has to be exceeded by our heart to get the blood to flow out of the heart and into vascular system How does exercise increase with preload? - Veno constriction - The SNS engages in the venous system that is holding the blood and causes the veins that are expanded and holding deoxygenated blood to constrict and get smaller to go up towards legs and back to heart - Skeletal muscle pump - Contracting skeletal muscle pushes blood upwards and towards the heart - Only go one direction - Respiratory pump - The diaphragm moving up and down causes a negative pressure in the thoracic cavity - The negative pressure is a suction that helps blood more upwards our heart What happens to ventricular contractility during exercise?  - Increases - We want to fill the ventricular with more blood and use actin and myosin to increase the amount ejected - Want to stimulate the muscle for more contraction How does exercise increase contractility? - Sympathetic stimulation - When we engage that muscle with sympathetic activity, there is a greater amount of blood ejected - Circulating epinephrine What happens to afterload with exercise? - Decreases - The increase will decrease the amount of blood that can be ejected at any given time during exercise - It is working against that contractility and the preload How does afterload impact stroke volume? - It decreases What impact does duration of exercise have on cardiac output, stroke volume and heart rate? - Cardiac drift - Heart rate increases - Cardiac output stays the same - Stroke volume decreases - Plasma volume via sweat decreases If there is less plasma in the blood what will happen to our ability during exercise to load that ventricle with blood? - It decreases since there isn’t has much blood - If stroke volume goes down then preload goes down - Heart rate is used for more blood to be pumped What impacts does endurance exercise training have on cardiac output? - It stays the same, they are able to exercise longer - A sedentary person and a trained person need to same amount of oxygen for the same amount of exercise How does heart rate and stroke volume influence these changes and lack of changes in cardiac output? - Heart rate decreases - Stroke volume doesn’t change How does chronic endurance exercise training increase stroke volume? - Increase in left ventricle chamber - Thicker wall with hypertrophy - Increase preload  - The amount of blood that comes back into the heart increases, the skeletal pump creates a negative pressure that occurs while breathing - Increase contractility - Decrease afterload - Blood pressure will lower, isn’t working against such a big pressure head What impact does endurance training have on oxygen consumption (VO2)? ↑ VO2max = CO ↑ x a-vO2 differ (=) VO2rest = CO (=) x a-vO2 differ (=) VO2submax = CO (=) x a-vO2 differ Which of these variables contributes more to the increase in maximal oxygen consumption? - They are both equal - Occur simultaneously and equally Is the endocardium is comprised of cardiac muscle? - No What is the endocardium made up of? - Endothelial cells The thickness of the left ventricular wall is what then the right ventricular wall? - Greater than Which is not a characteristic of cardiac myocytes? - Multiple satellite cells What are the characteristics of cardiac myocytes? - Single nuclei - Fibers branching - Single fiber type Lecture 13 What is total peripheral resistance (TPR)? - Resistance - Forces that act on blood in the direction of the relative fluid flow velocity - The walls of the vessels is what causes the resistance What physiological variables affect total peripheral resistance? - Viscosity, thickness of fluid - Diameter or radius - Length of the tube, longer wall = greater resistance Which variable in the Hagen-Poiseuille equation is most affected by exercise? - Radius How is length, viscosity, and radius (TPR) of the blood vessel affected by exercise? - Length is not affected - Blood vessels don’t get longer - Viscosity is minimally affected - Sweating which causes less plasma and more RBC  - Radius is affected the most - Blood vessels get bigger and smaller to accommodate more or less blood flow - Will dilate the working skeletal muscle and constrict the non working skeletal muscle (visceral) Which blood vessel type contributes the greatest amount to the regulation of TPR? - Arterioles - 70-80% of blood pressure is regulated within the arterioles What happens to TPR in the body during exercise? - Need to know the type of exercise to know if it increases or decreases - Dependent on the muscle mass activated and the intensity Why don’t we just calculate the mean blood pressure (MBP) as the sum of (SBP + DBP) /2? - The cardiac cycle isn’t split evenly - ⅓ of the time is the contraction phase - ⅔ of the time is the relaxation phase Why is it inappropriate to use the equation for mean arterial pressure (MAP) during exercise? - When we exercise the more the cardiac cycle decreases, mostly the resting phase - When exercising it is always changing and not always the ⅓ to ⅔ ration How is blood pressure regulated during rest? - Baroreceptors What is the average resting blood pressure? - 120/80 What are the two regulators for blood pressure? - Slow acting - Kidney through renin angiotensin system - Fast acting - Baroreceptors What are baroreceptors and where are they located? - Detect pressure to keep it normal - Carotid arteries - Aortic arch How does blood pressure decrease when it is too high? - ↓ sympathetic, ↑ parasympathetic - ↓ heart rate, ↑ artery dilation How does blood pressure increase when it is too low? - ↑ Sympathetic, ↓ parasympathetic - ↑ Heart rate, ↓ artery dilation What happens to systolic, diastolic and mean arterial blood pressure with exercise? - Systolic - Increase  - Diastolic - No change or slight decrease - Mean arterial blood pressure - Increase Why do baroreceptors not decrease blood pressure when exercising? - They reset to a higher limit - It will fight to maintain the blood pressure How does blood pressure change to DBP and SBP when using the equation? - ↑SBP = (↑)Q x TPR (=)or (↓small) ….CO? - (=)or(↓small) DBP = (=) Q x TPR (=) (↓small)...CO? How does blood pressure respond differently between arm exercise and leg exercise with similar workloads? - Takes the same amount of oxygen since it is the same workload - With arms, the body is dilating only ⅓ of the body and constricting ⅔ of the lower body - Higher blood pressure with arms - With legs, the body is dilating ½ of the body and constructing ½ of the lower body Where are baroreceptors located anatomically? - Carotid arteries and aortic arch What happens when baroreceptors are stretched as a result of increased blood pressure? - Increase parasympathetic nerve activity - Decrease sympathetic nerve activity - Reduce blood pressure True or false? During rest and exercise baroreceptors induced changes in blood pressure are primarily mediated by alterations in vascular conductance with only minimal contribution from cardiac output. - False Lecture 14 What is the vascular network? - Transports blood and nutrients the body What are the three networks with the vascular network? - Arteries - Veins - Capillaries What do arteries do? - Transport oxygenated blood away from the heart What do veins do? - Transport deoxygenated blood back towards the heart What do capillaries do? - It is the site of exchange and diffusion - Exchange nutrients and by products from metabolism like lactate What are the characteristics of arteries? - Thicker wall - More smooth muscle - More ability to regulate vascular tone - Allow to dilate and constrict What are the characteristics of veins? - Thinner wall - Less smooth muscle - Less ability to regulate vascular tone - Have a one way valve, to keep blood moving in one direction - Stores blood that comes back from capillaries - It can expand to store blood - When contracting muscles the blood will move up, when relaxing the blood will move down to the valve What are varicose veins? - Non-functioning veins - The flow will back up What is the distribution of the vascular network? - Aorta - Conduit arteries - Feed arteries - Arterioles - Capillaries - Venules - Veins - Vena cava What are arterioles and what do they do? - Site of resistance - Regulation of blood pressure and blood flow - Housed within the organ itself - Small change in size can make a big difference What are the different layers of a blood vessel? - Intima (inner) - Media - Adventia (outer) What is the intima made up of and what blood vessels have it? - Endothelium cells - Veins - Arteries - Capillaries What is the media made up of and what blood vessels have it? - Vascular smooth muscle - Arteries (have more) - Veins What is the adventitia made up of and what blood vessels have it? - Connective tissue - Arteries - Veins Why do capillaries not have a media or adventitia? - They can’t expand - It would be harder for diffusion to go through many different layers What does the intima do for blood vessels? - Release a substance to contract to dilate vessels - They can sense things going on and self regulate - They regulate vascular tone, atherosclerosis and angiogenesis - Synthesis and release of nitric oxide What is nitric oxide? - Production of more blood flow - Relaxes the blood vessels What does the media do for blood vessels? - Regulation of blood flow by contracting or relaxing the vessels with smooth muscle - Elastin sheets allow it to stretch and get bigger What does the adventitia do for blood vessels? - Nerves run through it - Serves as a structural integrity to keep its shape What happens to muscle blood flow when exercising? - Large increase in blood flow since it needs more oxygen - Modest increase of blood pressure - Large decrease in resistance, all of the arterioles in the working skeletal muscle are dilating in that region What happens to visceral blood flow when exercising? - Modest decrease in blood flow since we want more oxygen to go to the working skeletal muscle and not the organs - Modest increase of blood pressure - Large increase of resistance, all the arterioles that are feeding the organs constrict to go to the working skeletal muscle How does blood flow go up in skeletal muscle but down in visceral organs during exercise? - Functional sympatholysis What is functional sympatholysis?  - A release of metabolites and nitric oxide in response to exercise override sympathetic outflow and cause skeletal muscle arterioles to dilate - Shear stress of RBC moving through arterioles that are housed within the skeletal muscle itself to override the sympathetic outflow only within the working skeletal muscle and bind to vascular smooth muscle and causes it to relax - Overriding of the SNS in the active skeletal muscle to allow more blood flow How does endurance exercise training impact the vascular system? - Causes athlete arteries What are athlete arteries? - Increased skeletal muscle blood flow - Increased diameter of conduit arteries and arterioles - Decreased wall thickness - No change in vascular function What happens to arteries after one week of endurance training and their functional adaptations? - They increase - Due to hypertrophy, they are getting larger for more blood flow What happens to arteries after 16 weeks of endurance training and their functional adaptations? - There is no change in function because they get larger in size and don’t dilate as much since they are bigger What are the structural changes to vasculature? - After a week the tube gets bigger - After 16 weeks the tube gets even bigger - It gets bigger so it doesn’t have to dilate every time the person exercise to have greater blood flow Equations Fick equation (oxygen consumption) - VO2 = CO x a-vO2 diff Cardiac output - CO = HR x SV MAP (mean arterial pressure) - DBP + 0.33 (SBP -DBP) Resistance - TPR = (Length x viscosity) / Radius4 Blood pressure - BP = CO x TPR Blood flow - Q = Δ Pressure / Resistance Trained vs. Untrained Equation Rest Submax Max VO2 = = ↑ CO = = ↑ a-vO2 diff = = ↑ HR ↓ ↓ = SV ↑ ↑ ↑ What is the difference between an endurance trained person and a sedentary person with VO2? - Both start the same - A trained person can work longer due to having a higher capacity What is the difference between an endurance trained person and a sedentary person with cardiac output? - Start the same - A trained person is able to go longer, can put more blood longer What is the difference between an endurance trained person and a sedentary person with a-vO2 diff? - Trained person can last longer - Have a greater capillary network - Have a smaller distance for the blood to diffuse What is the difference between an endurance trained person and a sedentary person with max heart rate? - Stays the same due to max heart rate being 220-age What is the difference between an endurance trained person and a sedentary person with stroke volume? - A sedentary person can only reach 40% then plateau - The time for filling up the heart decreases - At 40% of VO2 they can’t increase the amount of blood being ejected - The blood rate is too high - Heart rate will increase - A trained person doesn’t plateau, they keep increase - Have to have a higher stroke volume to accommodate the lower heart rate What happens to blood pressure when increasing exercise? - SBP will increase - DBP will stay at a constant rate What happens to mean arterial blood pressure when exercising? - Will increase What happens to the arterial and venous blood to increase a-vO2 diff? - Venous blood will stay the same - Arterial blood will decrease since it is taking out oxygen from the blood What happens to venous oxygen contact with aerobic exercise? - Decreases - There is less oxygen since there are more capillaries - The venous content stays the same as a sedentary person, they are just able to pull off more oxygen making the venous levels go down What happens to arterial oxygen contact with aerobic exercise? - No change - You can’t increase something that is already at 100%