Collin County Community College BIOL 2401 Muscle Physiology 1 Muscle Length-Tension Relationship The Length-Tension Relationship Another way that muscle cells can alter their force capability, is determined by the length of the muscle cell. This usually comes into play when stretching muscle groups. The optimal resting length of a sarcomere is the length that generates maximal force. At this length ( 100% of muscle length), optimal overlap of myosin thick filaments exists with the thin actin filaments. Thus maximal cross bridge formation occurs between myosin thick filaments and actin thin filaments! 2 1
Tension Development at Muscle Cell The Length-Tension Relationship Stretching a muscle ( greater than 100% muscle length), pulls the actin filaments away from the myosin filaments, resulting in an increasing number of myosin heads with no actin to attach to - it results in a decline in tension development When a muscle is pushed together ( less than 100% muscle length), actin filaments tend to overlap and interfere with each other for cross bridge attachment and tension development drops. 3 Tension Development at Muscle Cell The Length-Tension Relationship 4 2
Energy Metabolism Energy metabolism deals with all the components and processes within a cell that interact to provide the necessary energy to the energy consuming elements of a cell. The energy requiring processes in a muscle cell are of course those that consume ATP e.g. the contractile elements. A contracting muscle cell requires about 2500 ATP molecules per second. However, ATP is a very unstable component. The cell only has a small quantity available for direct use. 5 Energy Metabolism So how does a muscle cell deal with continued demand during contraction? Three different processes are involved and provide the ATP needed for contraction. Aerobic Metabolism Glycolysis Creatine Phosphate System 6 3
Energy Metabolism 1. Aerobic respiration This is the process where the energy of nutrients is completely released by means of several metabolic pathways. The final process occurs in mitochondria where, in the presence of oxygen, ATP is formed It requires the continuous delivery of oxygen and nutrients to the tissues and cells ( thus requires an efficient and non-occluded blood vessel network to the tissues) 7 Energy Metabolism C 6 H 12 O 6 + 6 O 2 + 38 ADP + 38 Pi 6 CO 2 + 6 H 2 O + 38 ATP The typical nutrient is glucose (6 carbon molecule). comes from the diet from stored glycogen ( animal equivalent of starch) Steps in Aerobic Metabolism & Oxidative Phosphorylation Glucose is oxidized in glycolysis to Pyruvate Pyruvate enters the mitochondria and is completely oxidixed to CO 2 in the Krebs Cycle. Energy (electrons and H + ) is transferred onto NAD + and FAD +, forming NADH and FADH NADH and FADH go through the electron transport chain and ATP is generated via proton gradients and the ATPsynthase. The final electron acceptor in the ETC is oxygen! 8 4
Energy Metabolism O 2 used in this process 9 Energy Metabolism 2. Anaerobic Glycolysis In the absence of oxygen, the mitochondria can t oxidize the pyruvate. The pyruvate is converted into lactic acid by means of Lactic Acid Dehydrogenase (LDH) Occurs in muscles with a high energy demand ( usually during vigorous activity). Depending on the muscle type, exercise results in the muscle to bulge up which constrict the blood supply to the muscles. This reduces blood flow and reduces oxygen and nutrient supply. The lack of oxygen deviates the aerobic pathway into a lactic acid producing pathway. 10 5
Energy Metabolism x No O 2 - no ETC activity-no Kreb cycle turnover-pyruvate not used in Mitochondria x no x no Lactic Acid production 11 3. Creatine Phosphate Energy Metabolism Creatine Phosphate is a high energy reservoir made from ATP and creatine, catalyzed by the enzyme Creatine Kinase ATP + Creatine ADP + CrP Creatine Kinase (or Phosphocreatine Kinase) is an equilibrium enzyme ; the reaction it catalyzes is driven by mass action ratios. In other words, if ATP increases, the reaction is driven to the right, making CrP. If ATP decreases (or CrP increases), the reaction is driven to the left, making ATP. 12 6
Energy Metabolism 13 Creatine Phosphate helps to buffer changes in ATP during bouts of high energy demands. ATP +H 2 0 CrP + ADP CrP + H 2 0 Rest ADP + P i ATP + Creatine P i + Creatine 1 minute heavy exercise Concentration CrP ATP P i CrP ATP P i 14 7
Energy Metabolism Summary During resting conditions, oxygen supply is plenty and energy demands are low. Most energy is supplied by Ox.Phos. In addition, muscle converts extra ATP into CrP and extra glucose into Glycogen During increased demands of energy, such as increased contractile activity, demand may outpace production via Ox.Phos. At this point, glycolysis and CrP system will be used more in order to meet the demands. At highest activity and demand, most energy will come from glycolysis and production of lactic acid will increase. Glucose will be provided by breakdown of the glycogen reserves. CrP will be exhausted quickly and continued activity depends on glycogen stores and the efficiency in getting rid of lactic acid. 15 Energy Metabolism Summary 16 8
Energy Metabolism Most muscles have poor supply of mitochondria. Their capacity to generate ATP via oxidative phosphorylation is thus limited. Muscles thus will generate Lactic acid quite fast when very active. 17 Energy Metabolism The Cori cycle Lactate formed by active muscle is dumped into the blood stream and directed to the liver. Here it is converted back into glucose, and re-enters the bloodstream. This cycle shifts part of the metabolic burden of active muscle to the liver and prevents muscle acidification. 18 9
Energy Metabolism and Exercise Aerobic endurance refers to the length of time muscle contraction uses aerobic metabolism. Anaerobic metabolism refers to the moment oxygen becomes limiting. In general, activities that depend on anaerobic metabolism cannot be sustained for prolonged periods of time! The shift from aerobic to anaerobic is when lactic acid start to accumulate in muscles. 19 Energy Metabolism and Exercise Energy Source Initial Amount Enough for ATP Stored 3 mmoles 2-5 sec CrP Stored 20 mmoles 10-15 sec Glycolysis (anaerobic) Via Stored Glycogen 100 mmol ~ 130 sec Aerobic Via Stored Glycogen and contineous supply of O2 and glucose ~ 40 min and more Prolonged activity is thus only possible by means of oxidative respiration and metabolism (and a good supply of blood (for O2) and nutrients (via blood or internal glycogen stores) 20 10
Energy Metabolism and Exercise O 2 demand and Exercise The higher our activity level, the more ATP needed by the muscles for contractile force production. This is reflected in a higher Oxygen consumption (VO 2 ) since O 2 is used by the mitochondria in the process of making ATP (oxidative phosphorylation)! The more ATP needed, the more active the mitochondria, and the more oxygen they require and consume. When mitochondria cannot supply more ATP, we have reached the anaerobic threshold (arrow); at that point more energy supply comes from anaerobic metabolism. 21 Skeletal Muscle Types Skeletal muscles can be classified into three broad groups based on : Speed of contraction Resistance to fatigue Fast twitch glycolytic muscle fibers Fast twitch oxidative muscle fibers Slow twitch oxidative muscle fibers 22 11
Skeletal Muscle Types Speed of contraction is determined by the isoform of myosin ATPase! The faster the ATPase splits ATP, the faster a cross bridge cycle can be accomplished. This translates into faster tension developments! (the steeper the upwards slope of the graph, the faster the tension developed ). 23 Skeletal Muscle Types Fast twitch muscle fibers also pump Ca 2+ faster back into the S.R., which thus indicates a faster Ca 2+ - pump as well. This translates into shorter twitch duration due to a faster relaxation. Contraction in Fast twitch muscle fibers lasts about 7.5 msec while Slow Twitch fibers last 10 times as long. 24 12
Skeletal Muscle Types Fatigue is primarily determined on how well the muscles can generate and maintain ATP levels. Tissues with low mitochondrial density typically can not provide a quick supply of readily available ATP! 25 Skeletal Muscle Types Slow twitch oxidative muscle fibers (also called Type I fibers or red muscle fibers) rely on aerobic metabolism for ATP. Contain many mitochondria Contain good blood supply with dense capillaries Contain myoglobin ( = muscle pigment that binds oxygen (similar to hemoglobin in blood) which helps in the oxygen supply and transport to the mitochondria. Since they contract slowly and have good supply of oxygen, they are fatigue resistant (don t run out of ATP). Examples : muscle used for maintaining posture, standing 26 13
Skeletal Muscle Types Fast twitch glycolytic muscle (also called Type II-A fibers or white muscle fibers) rely mostly on glycolysis for ATP. They contain relatively few mitochondria. They contain poor blood supply They contain a good store of glycogen Run out of ATP faster and produce lactic acid, resulting in acidification Fast glycolytic muscle thus fatigue easily. Examples : biceps 27 Skeletal Muscle Types Fast twitch oxidative muscle fibers (also called Type II B fibers or intermediate fibers) rely on glycolysis and aerobic metabolism for ATP. They are sort of an intermediate muscle They resemble Type II A fibers in that they have little myoglobin (pale looking muscles). They resemble Type I fibers in that they have intermediate mitochondrial density and capillaries. They are thus intermediate with respect to fatigue as well. Depending on exercise and training, they will gain more mitochondria and more capillaries will supply these muscles 28 14
Slow-oxidative skeletal muscle responds well to repetitive stimulation without becoming fatigued; muscles of body posture are examples. Fast-oxidative skeletal muscle responds quickly and to repetitive stimulation without becoming fatigued; muscles used in walking are examples. Fast-glycolytic skeletal muscle is used for quick bursts ofstrong activation, such as muscles used to jump or to run a short sprint. 29 Skeletal Muscle Types 30 15
Skeletal Muscle and Fatigue Origins of fatigue Depletion of energy stores (ATP, CrP, glycogen) Accumulation of Pi due to breakdown of CrP Accumulation of H + due to breakdown of ATP and production of lactic acid Accumulation of K + in the T-tubules, resulting in Action Potential conduction failure Synaptic fatigue : motor axon terminal runs out of ACh Central Command fatigue : psychologically tired 31 16