Muscle Physiology Stimulus Frequency and muscle contraction Energy

Muscle Physiology -Stimulus Frequency and muscle contraction -Energy requirements for muscle -Types of muscle fibers

Muscle twitch • Contraction of a whole muscle in response to a stimulus that causes an action potential in one or more muscle fibers. – The normal function of muscle is more complex, however, but an understanding of the muscle twitch makes the function of muscles in living organisms easier to comprehend. • Is usually the contraction of all muscle fibers in a a motor unit in response to a stimulus • Represented by 3 phases lag phase (latent period), contraction, relaxation

Muscle twitch Lag (latent) phase Is the time period b/w application of the stimulus to the motor neuron and the beginning of contraction. Contraction phase Is the time during which contraction occurs Relaxation phase Is the time during which relaxation occurs

Events during each phase of a muscle twitch in response to a single action potential (AP) in the motor neuron • Lag phase or latent period – AP propagated to presynaptic terminal, synaptic vesicles fuse and release ACh into cleft, ACh diffuses & binds to ACh receptors on sarcolemma (postsynaptic membrane). – ACh is rapidly degraded in the synaptic cleft, thus limiting the length of time ACh is bound to its receptor. The result is that one presynaptic action potential produces one postsynaptic action potential in the muscle fiber. – The AP spreads along the sarcolemma of the muscle fiber and into the T-tubules. The electrical change that occurs in the T-tubule in response to the AP make the membrane of the SR very permeable to Ca ++. Ca++ diffuses from the SR into the sarcoplasm. – Ca++ binds to troponin and the troponin/tropomyosin complex changes its position and exposes active sites on the actin myofilaments.

Events during each phase of a muscle twitch in response to a single action potential (AP) in the motor neuron • Contraction phase – Cross bridges b/w actin molecules and myosin molecules form, move, release, and reform many times, causing the sarcomere to shorten. – ATP must be bound to the myosin molecule for crossbridge formation and after crossbridge movement is complete, another ATP must bind to myosin to allow cross bridge release.

Events during each phase of a muscle twitch in response to a single action potential (AP) in the motor neuron • Relaxation phase – Ca++ are actively transported into the SR. – The troponin-tropomysin complex inhibit cross bridge formation. – The muscle fibers lengthen passively

Muscle twitch and multiple wave summation due to stimuli of increased frequency Complete tetany (5) Complete relaxation b/w stimuli (1) Incomplete tetany (2 -4) Stimuli of increasing frequency. Stimuli 1 -4 allow some degree of relaxation b/w stimulus application. Stimulus 5 leads to tetanus where there is sustained contraction in the face of repetitive stimuli that is so rapid that there is no relaxation

Strength of muscle contraction • The increased force of contraction produced in summation and tetanus occurs b/c 1. there is not enough time b/w contractions for muscle fibers to completely relax and there is a buildup of Ca++ in myofibrils, which promotes cross-bridge formation and cycling. 2. the rapid production of AP in the muscle fibers causes Ca++ to be released from the SR faster than they are actively transported back into the SR.

Strength of muscle contraction • The increased force of contraction produced in recruitment occurs b/c 1. of increased numbers of muscle fibers contracting due to increasing the number of motor units stimulated 2. as the number of motor units stimulated increases, more muscle fibers are stimulated to contract and the force of contraction increases. Maximum force of contraction is produced in a given muscle when all the motor units of that muscle are stimulated (recruited).

Stimulus Strength and Muscle Contraction • All or None principle: – States that once a stimulus is applied to an individual muscle fiber it will contract to its greatest extent or not at all. Any further increase in the degree of stimulation (after the threshold stimulus is reached) will not cause a corresponding increase in muscle contraction. – The weakest stimulus capable of causing a contraction in the muscle fiber is called a threshold stimulus – A stimulus not capable of inducing a contraction is called a subthreshold stimulus

Muscle Metabolism • The chemical energy released by the hydrolysis of ATP is necessary for both muscle contraction and muscle relaxation. • Muscles typically store limited amounts of ATP – enough to power 4 -6 s of activity. – So resting muscles must have energy stored in other ways.

Resting Muscle and the Krebs Cycle • Resting muscle fibers typically take up fatty acids from the blood stream. – How might they enter the cell? – Inside the muscle fiber, the FA’s are oxidized to several molecules of a compound called Acetyl-Co. A. This oxidation will also produce several molecules of NADH and FADH 2. – Acetyl-Co. A will then enter a cyclical series of reactions known as the Krebs cycle or Tricarboxylic Acid cycle. – In the Krebs cycle, acetyl-Co. A combines with the compound oxaloacetate and then enters a series of rxns. The end product of these rxns is CO 2, ATP, NADH, FADH 2, and oxaloacetate (thus we call it a cycle)

Krebs Cycle Products Oxaloacetate will simply combine with another molecule of acetyl-Co. A and reenter the cycle. NADH and FADH 2 will enter another series of rxns known as the Electron Transport Chain (ETS). These rxns occur along the inner membrane of the mitochondrion. They basically consist of the passing of electrons from compound to compound with energy being released each time and used to drive the synthesis of ATP. The final electron acceptor is oxygen when it combines with 2 hydrogen atoms to yield water.

Krebs Cycle Products • CO 2 will diffuse out of the mitochondria, out of the muscle fiber, and into to the blood stream, which will take it to the lungs. • The ATP made in the Krebs cycle plus the ATP made during the ETC will be used in many ways. – See if you can list at least 5!

ATP Use in the Resting Muscle Cell • ATP is necessary for cellular housekeeping duties. • ATP powers the combination of glucose monomers (which have been taken up from the blood stream) into the storage polymer glycogen. • ATP is used to create another energy storage compound called creatine phosphate or phosphocreatine: ATP + Creatine ADP + Creatine-Phosphate this rxn is catalyzed by the enzyme creatine kinase

Energy Requirements for Muscle Contraction • Muscles can’t store/stockpile ATP in preparation for periods of activity, but can store the high-energy molecule creatine phosphate. • Creatine phosphate (CP) provides a means of storing energy that can be used rapidly to help maintain an adequate amount of ATP in a contracting muscle fiber.

Energy Requirements for Muscle Contraction • ATP is produced continually in mitochondria located in the sarcoplasm b/w myofibrils in both resting and active muscles. • Excess ATP in an inactive muscle is used to synthesize CP. • In an active muscle, the small pool of ATP is preferentially used then the energy from CP helps to restore the ATP pool

Fate of ATP in resting and active muscle

Working Muscle • With the onset of exercise, almost immediately our stored ATP is depleted. • For the next 15 seconds or so, we turn to the phosphagen system, a. k. a. , the energy stored in creatine-phosphate. Creatine-P + ADP Creatine Kinase Creatine + ATP – The ATP is then available to power contraction and relaxation: myosin ATPase, Ca 2+ ATPase in the SR membrane, and Na+/K+ ATPase in the sarcolemma. – The phosphagen system dominates in events such as the 100 m dash or lifting weights.

Working Muscle • After the phosphagen system is depleted, the muscles must find another ATP source. • The process of anaerobic metabolism can maintain ATP supply for about 45 -60 s. • Anaerobic means “without air, ” and it is the breakdown of glucose without the presence of oxygen. – It usually takes a little time for the respiratory and cardiovascular systems to catch up with the muscles and supply O 2 for aerobic metabolism.

Anaerobic Metabolism • Glucose is supplied by the breakdown of glycogen or via uptake from the bloodstream. • Glucose is broken down into 2 molecules of pyruvic acid, with the concomitant production of 2 ATP and the conversion of 2 molecules of NAD+ into NADH. This process is known as glycolysis and it occurs in the sarcoplasm. – Unfortunately, w/o O 2, we cannot use the NADH in the ETC. – In order for more glycolysis to proceed, the muscle cell must regenerate the NAD+. It does this by coupling the conversion of pyruvic acid into lactic acid with the conversion of NADH into NAD+

Anaerobic Metabolism • Lactic acid typically diffuses out of muscles into the blood stream and is taken to the liver, kidneys, or heart, which can use it as an energy source. • Anaerobic metabolism is inefficient. Large amounts of glucose are used for very small ATP returns. Plus, lactic acid is a toxic end product whose presence contributes to muscle fatigue. • Anaerobic metabolism dominates in sports that requires bursts of speed and activity, e. g. , basketball.

Aerobic Metabolism • Occurs when the respiratory and cardiovascular systems have “caught up with” the working muscles. – Prior to this, some aerobic respiration will occur thanks to the muscle protein, myoglobin, which binds and stores oxygen. • During rest and light to moderate exercise, aerobic metabolism contributes 95% of the necessary ATP. • Compounds which can be aerobically metabolized include: – Pyruvic acid (made via glycolysis), fatty acids, and amino acids.

Aerobic Metabolism • It occurs in the mitochondria. • Pyruvic acid from glycolysis is the primary substrate, but the cell may utilizes fatty acids and amino acids. • Aerobic respiration typically yields 36 ATP per molecule of glucose. Compare this to anaerobic metabolism.

Immediate source of energy (ATP) for muscle contracion • Anaerobic respiration-occurs in the absence of oxygen and results in the breakdown of glucose to yield ATP and lactic acid. – Less efficient but is faster, especially when O 2 availability limits aerobic respiration – May utilize many glucose molecules to produce many ATPs for a short period of time • Aerobic respiration-requires oxygen and breaks down glucose to produce ATP, CO 2 and water. – More efficient than anaerobic respiration (18 times more ATP from 1 glucose molecule theoretically) – Utilizes a greater variety of molecules as energy sources (eg fatty acids and amino acids can be used to generate ATP)

Muscle Fatigue • Physiological inability to contract • Results primarily from a relative deficit of ATP. • Other contributing factors include the decrease in sarcoplasmic p. H (what causes this? ), increased sarcoplasmic [ADP], and ionic imbalances.

Oxygen Debt • Refers to the fact that post-exercise breathing rate >>> resting breathing rate • This excess oxygen intake serves many tasks: – Replenish the oxygen stored by myoglobin and hemoglobin – Converts remaining lactic acid back into glucose – Used for aerobic metabolism to make ATP which is used to: • Power the Na+/K+ pump so as to restore resting ionic conditions within the cell. • Replenishes creatine phosphate and glucose from lactic acid – Replenish the phosphagen system – Replenish the glycogen stores

Oxygen Debt • Occurs as a result of intense exercise – The rate of aerobic metabolism will remain elevated for a period of time following anaerobic exercise to “pay back” or rejuvenate depleted energy sources. • Magnitude of debt depends on intensity, length of time sustained and physical condition of individual (i. e. the capacity to perform oxidative metabolism is not as great as in a well-trained athlete)

Slow/Fast fibers 2 types: • Fast twitch- contract quickly and fatigue quickly • Slow twitch-contract more slowly and are more resistant to fatigue • Note: Not all skeletal muscles have identical functional capabilities. The proportion of muscle fiber types differs within individual muscles.

Slow-Twitch muscle fibers type I • Contract more slowly, are smaller in diameter, have a better developed blood supply, have more mitochondria are more fatigue resistant than fast twitch fibers • Aerobic metabolism is primary source for ATP and their capacity to use this pathway is enhanced by plentiful blood supply, the presence of numerous mitochondria and large amounts of myoglobin

Fast-Twitch muscle fibers type IIa and type IIb • Contain myosin molecules that breakdown ATP more rapidly than slow-twitch fibers – Increase rate of crossbridge formation, release, and reformation (cycling) – Type IIb contract 10 x faster than type I fibers – Type IIa contract at an intermediate speed and are more fatigue resistant than type IIb fibers. • Associated with a less well-developed blood supply, lower levels of myoglobin and fewer and smaller mitochondria • Possess large deposits of glycogen and are well adapted to perform anaerobic metabolism. – Contract rapidly for a shorter time and fatigue relatively quickly and are not adapted for supplying large amounts of energy for a prolonged period

Distribution of fiber types • humans exhibit no clear separation of slow -twitch and fast twitch fibers in individual muscles (e. g. in a chicken white meat is found in the breast and dark meat is found in the legs) • In humans, most muscle have both types of fibers, although the number of each varies in a given muscle. – Larger postural muscles contain more slow twitch, whereas muscles of the arms contain more fast twitch fibers.

Distribution of fiber types • Distribution is established developmentally and does not change much for each individual – Sprinters-greater % of fast-twitch fibers in legs – Long distance runners-higher % of slow-twitch fibers in legs Note: One type of fiber can be converted to another type, with specific training. With wt training some type IIb can be replaced by IIa myosin myofilaments. Vigorous exercise programs can also cause a limited number of type I myofilaments to be replaced by type IIa myofilaments. Training can also increase the capacity to perform more efficiently (e. g. aerobic metabolism can convert fast twitch muscle fibers that fatigue readily to fast-twitch fibers that resist fatigue by increasing # of mitochondria and increasing the blood supply or slow twitch muscle fibers can be increased in size or the muscle vascularity may be increased)

Effects of exercise • Muscles increase in size (hypertrophies), strength and endurance in response to exercise…Why? – Fibers increase in size # of myofibrils and sarcomeres increase within each muscle fiber • (muscle cell # does not change appreciably during a person’s life) – Blood vessels, connective tissue and mitochondria increase – Nervous systems ability to activate greater numbers of motor units simultaneously and improvements in neuromuscular coordination strengthen muscle – Trained muscle is less restricted by excess fat and metabolic enzymes increase in hypertrophied muscle fibers and lead to greater capacity for ATP production – Improved metabolism, increased circulation to exercising muscle and increased numbers of capillaries, more efficient respiration, and a greater capacity for the heart to pump blood in part improves endurance