Muscle Physiology

types of muscle:

Cardiac muscle: unique to the heart. drives circulation and maintains blood pressure

cardiac muscle structure

  1. have branching interconnecting cells
  2. direct electrical connections

   

  1. incalcated discs
  2. desmosomes
  3. gapjunctions
    1. many mitochondria
    2. internal/external membranes specialized

Cardiac muscle function

  1. automaticity

   

  1. pacemaker cells
    1. nervous control of

   

  1. pace
  2. contractile force not contraction
    1. 10x prolonged contraction cycle
    2. no tetanus
    3. streching increases contractile force frank starling principle

smooth muscle: moves material through tubular organs. controls diameter of tubular organs

skeletal and cardiac muscle are striated muscle while smooth is unstriated. skeletal muscle is voluntart and cardiac and smooth muscle are involuntary.

Major function of skeletal muscle

  • movement: muscle attaches directly or indirectly to the bone
  • maintain posture/ body position: muscle continuously contraract to make adjusments to maintain posture
  • stabilize joints: tendons cross joints and muscle tone
  • thermogenesis: generate heat when contracting

Skeletal mucscle anatomy

fasicales: are the bundels in the muscle l within the bundels we have a muscle fiber. inside of the muscle fiber we have some thing called a myofibril (contractile organelles). myofibrils are packed with contractile protines that are arranged in a sarcomere

muscles are made up of muscle cells called muscle fibers. muscle fibers are packed full of long fiberlike contractile organelles called myofibrils. myofibrils are made up of contractile protines called myosin and actin which are organized into units called sarcomeres.

Sliding filament model

Resting sarcomere: {Ca++] low in the sarcoplasm, myosin bonds are hidden. myosin heads are cocked they have bound ATP and split it to ADP+Pi

step 1: Ca++ induces exposure of active sites

[Ca++] high in the sarcoplasm, TN binds Ca++shifts Tn+Ty laterally, myosin binding sites on actin are exposed myosin heads are still cocked

step 2: cross bridge attachment

[Ca++] high in sarcoplasm. myosin heads bind to actin. myosin heads are still cocked

Step 3: Power stroke

[Ca++] high in the sarcoplasm, actin myosin binding triggers head to expel ADP+Pi. Myosin heads release stored energy: drive actin myosin sliding

Step 4: detachment: [Ca++] high in sarcoplasm. myosin binds a new ATP: actin is released

Myosin and actin

myosin makes up thick filaments while actin makes up the thin filaments. myosin and actin are arranged in very specific overlapping patter in the sarcomere.

  • the Z-line is the end of the sarcomere this is where actin attaches to adjoining sarcomeres ( from z-line to z-line is a sarcomere)
  • A Band (dark band) streaches from end to end of myosin, contains both acting and myosin filaments
  • I Band (light band) is space between myosin that only contains actin
  • H Zone is a non overlapped region of myosin only there is no actin
  • M-line: center of sarcomere hilding adjacent myosin together with supporting protines

Myosin contians headgroups that want to grab onto the actin. the sarcomere is the contractile unit of the muscle cell.

Myosin forms thick filaments. the myosin heads contain binding sites for the actin and the myosin wants to grab onto the actin. the myosin heads also contain an ATPase site which can activate the myosin. actin forms thin filaments, actin has myosin binding sites, where myosin wants to grab onto the actin. actin protine binds together to make the thin filaments. there are two regulatory protines found on actin those are troponin and tropomyosin

  • Tropomyosin binds to actin and blocks the myosin binding sites on actin. it looks like a rope and covers the myosin binding sites
  • troponin binds to the tropomyosin and locks it onto the actin looks like beads.

think of these as a chastity belt the myosin heads want to bind to the actin but tropomyosin prevents that binding site from being available so it wraps around and troponin is like that lock that locks the chastity belt closed so that the actin is not available.

when a muscle cell is relaxed its individual myofibrials are also relaxed. this causes the actin to be streched further away. when a muscle is relaxed we have a large H zone. when you contract a muscle the indiviudal protines will change and the actin is going to move closer to the M line making the H zone very small. that also makes the I band shorter. everything moves in during contraction. contraction is the shortening of sarcomeres within the myofibrils and the total shortaning of the muscle cell its self.

During contraction:

  • H zone is smaller
  • I band is smaller
  • moves the Z line closer together
  • A band and M line do not change this is because only the zones that have actin change

Excitation contraction coupling

this is muscle contraction that is caused by deporlaization (activation of the muscle cell) of the muscle cell which leads to the movement of actin “sliding” over myosine to cause a contraction

  1. action potential: reaches the muscle fiber (comes from the nervous system)
    • reaches the muscle cell membrane
    • the action potential comes from the motor neuron which contracts the muscle at the neuromuscular junction
    • acetylcholine is released and the muscle membrane is depolarized
    • a neuromuscular junction is the contact that is made between the motorneuron and a muscle fiber
    • the action potential reaches the cell membrane through the acetylcholine release at the neuromuscular junction
    • action potential travels down the motor neuron the neurotransmiter is released and binds to the acytlcoline receptors, the acetylcholine receptors are ion channels so when the neuro transmitter binds to the receptor it opens up ion channels and sodium rushes into the muscle cell membrane when sodium rushes into the muscle cell membrane that then causes electrical activity or action potential traveling into the muscle cell itself. that action potential in the muscle cell is then going to make changes within the muscle cell (calcium relase)
  2. Calcium release: Ca2+ is released
    • depolarization of the muscle cell membrane cause calcium release
    • depolarization spreads into membrane regions called transverse tubules (t-tubules)
    • T-tubules contact the sarcoplasmic retuculum
    • the sarcoplasmic reticulum is a modified endoplasmic reticulum that stores Ca2+ and contains Ca 2+ channels
    • calcium is relased from the sarcoplasmic reticulum into the cytosol of the muscle cell
    • the depolarization of sodium traveling down the membrane is transmitted down the T tubules and then reaches the sarcoplasmic reticulum. the sarcoplasmic reticulum is a modified endoplasmic reticulum. it is a branching network of membranous orgnaelle that stores calcium. once the depolarization of sodium travels down the T tubules then calcium will be release from the sarcoplasmic reticulum
  3. troponin activated: Ca2+ binds to troponin (activated by calcium)
    • calcium activates troponin, troponin normally holds tropomyosin onto actin
    • troponin responds to Ca2+ entery and releases from tropomyosin and actin
    • calcium activates tropoin, when calcium binds to the troponin the troponin “unlocks” and releases from the tropomyosin.
  4. tropomyosin released: troponin pulls tropomyosin off of myosin binding sites
    • once the calcium releases form the tropomyosin, tropomyosin is moved out of the way exposing the actin binding site and making them available. now the myosin heads are able to bind specifically to the actin because the tropomyosin is not blocking anymore. tropmyosine is released freeing the actin
  5. cross bridge: myosin heads grab onto actin cross bridge forms
    • myosin heads bind to actin formin a cross bridge. when the myosine heads bind to the actin we form whats called a cross bridge. that binding is called cross bridge formation
  6. power stroke: myosin heads pill actin inward using “power stroke”
    • the myosin heads move the actin like a rachet moving the actin in wards tword the midline this is called the power stroke and it requires ATP
  7. reset: myosin detaches from actin and resets
    • myosine moved the actin in a powerstroke now the myosin has to detach and rest and get ready for another contraction. that detaching a resting also requires ATP
  8. calcium is returned to the sarcoplasmic reticulum
    • calcium pumps return calcium to the sarcoplasmic reticulum to stop the signal, reset calcium and prepare for the next contraction
    • calcium is returned to the sarcoplasmic reticulum, there are calcium pumps located in the sarcoplasmic reticulum that stops the calcium signal and the resets the calcium also to prepare for the next contraction

Sliding filament theory: the mechinism of myosin heads “sliding” actin tword the center of the sarcomere is based on the sliding filament theory

calcium is the excitation signal, required to free the myosin binding sites. lack of calcium or low calcium levels and depletion of calcium in a muscel can cause the muscle to weaken. if there is no calcium in the mucle cell you will not have the release of troponin and you will not have the myosin binding to the actin the muscle cell will then be unable to contract

  • lack of calcium= no binding mucle is relaxed

ATP is required for power stroke

ATP is also required for cross bridge release if theres a lack in ATP there is no release. upon death, no ATP us available rigamortis (state of constant fixed contraction) sets in. no recycling of the ATP theres no release of the muscle

  1. myosin head is energized an ready to bind to actin if calcium is present the troponin is unlocked tropomyosin moves out of the way and the myosin can bind to the actin
  2. after that binding the myosin head then ratchets and moves the actin over during the power stroke
  3. another ATP is then required for the detachment of the myosin and the re-energizing to prepare for the next step. if there is not fresh ATP available then we form this rigor complex or rigor mortis in which the muscles are stuck in a contracted cross-bridge power stroke state

Phase of muscle contraction

latent period- first few milliseconds, excitation-contraction coupling

period of contraction- cross bridge cycling, tention increases

period of relaxation- calcium transported back into the SR cross bridge cycling ends, tension decreases

stimulus and delay then there is a period of contraction where the muscle is actually responding finally there’s a period of relaxation

Muscle mechanics

within a whole muscle, several muscle fibers will contract to create movement. A single muscle contraction is called a twitch muscles are surrounded by connective tissue extending into elastic tendons which attach the muscle to the bone. contracting the muscle creates tension which stretches the tendon and applies force to move the bone. the bone itself and anything being held near the bone have weight called the Load which will oppose the movement

types of muscle contraction

muscle contraction causes shortening is a concentric contraction

muscle contraction used as a stabilizing contraction is used as a stabilizing contraction muscle actually lengthens is called Eccentric contraction

Isotonic contraction: load remains constant, the muscle shortens load is too heavy force cannot overcome the load

Isometric Contraction: tension develops but is done and load is not moved

Factors affecting muscle tension

  • motor unit recuritment

  base line muscle tone: some muscle fiber are always active to maintain muscles even when no movement is taking place.

  motor unit recruitment: activation of more motor units to increase tention in the muscle as the load increases and more force is needed

  If we want to increase the strength of the muscel then we have to reqruit more neurons activate more motor neurons to activate more muscle cells. if we activate more motor neurons we will then activate all the muscle cells its attached too. this is called motor neuron recutment this will increase tention in the muscle as the load increases. the more motor units recruited the stronger the contraction

  • size of the muscle

  -the number of muscle fibers per motor unit this is determined by development and the general size of the muscle

  -size of individual muscle fibers- fibers produce more myofilaments in response to demands placed on them with training muscle cell will widen in diameter

  -fibers hypertrophy when not used (increase in muscle cell size)

  -bigger muscles have more fibers per motor neuron there is a limit in the how much a smaller muscle can contract compared to a larger muscle

  • muscle twitch simulation

  -a single action potential in a muscle fiber produces a muscle twitch

  -repeated simulation is needed to produce sustained and longer duration contractions of muscles

  -muscle fibers can respond to repeated stimuli before they are fully relaxed this is called twitch summation

  Calcium enters calcium is pumped back. repeated stimulation is needed to sustain a longer duration contraction that twitch is not enough to produce anything significant with respect to movement. we need a long sustained and held contraction we do this by stimulating the muscle very close in time. when we stimulate a muscle close in time it causes for calcium to build up and as calcium builds up and we give calcium time to go back into the sarcoplasmic reticulum we’ll get summation or addition of activity. (addition of contractions on top of eachother we can do this to the extreme were we deliver very very close together summation to the point where there’s absolutely no chance for the calcium to return back to the sarcoplasmic reticulum and you just dump a whole bunch of calcium onto the sarcomere with no possibility of relaxation, when you do this with a very high frequency youwill get a long smooth sustained contraction this is tetanus

  • tetanus

  -a muscle fiber at maximum stimulation with no relaxation will reach a sustained maximal contraction called tetanus

  -tetanus will last until the muscle becomes fatigued

  you want tetanus in skeletal muscle if your trying to hold an action and get some sustained force of contraction it will hold them until the stimulation stops or until the muscle is fatigued

  • the treppe (stair effect )

  treppp- increased contraction in response to multiple stimuli of the same strength

  -different that summation because relaxation occurs contractions increase because

  • there is increasing availablity of Ca2+ in the sarcoplasm
  • reduced slack of the elastic series component
  • muscle enzyme systems become more effcient because heat is increased

  the treppe effect aka the staircase effect and this is increased contraction in response to multiple stimuli of the same strength this is different from summation becuase relaxation occurs as theres increasing availablity of calcium but the calcium is able to get pumped back to the SR. think of this as “warming up” the first time it happens calcium is pumped in then it goes back down. the second time more calcium is pumped in then it goes back down, etc… contractions increase because you will get sort of an enhancement of the elastic component of the muscle and as you increase heat “warm up” the muscle the enzymes increase to make the contraction stronger. calcium in calcium out, somehow with the repeated use of a muscle and increase in heat increse in calcium from the SR and more optimal elastic component then we will get the “stair case effect”

  • optimal length

  -myosin heads occupy only a certain range of length of the sarcomere beyond that only myosin tails are present

  -optimal length of a muscle is a range at which maximal crossbridges are possible'

  this comes into play when someone has strained or torn a muscle generally development is set up such as muscles are alredy at thier optimal length but this is comes back to cross bridge formation. where every myosin head is there is an actin nearby for it to grab onto, so the optimal amount of myosin and actin interaction at optimal length. if the muscle is streched too far then the myosin is too far from the actin and even thought the actin binding sites are avialable the myosin cant reach them to grab on so this will not provide much strenght in the muscle contraction if there too close there is no where for the actin to go to create a chain and to produce tention so the actin is already as close as it can possibly can get, the myosin can pull on it but its not going to make any difference in the tension optimal length of the muscle is important for maximizing cross bridge formation

motor units

all muscle fibers within a whole muscle are mo t active during every contraction. its not going to use all the strength at once. it will use the strength depending on the load. not all muscle fibers activated by the same motor neuron

a small subset of muscle fibers will be activated based on need

the smallest subset is a motor unit: one motor neuron and all the muscle muscle fibers it innervates

Muscles require ATP

several ATP are required for a full cycle of excitation/ contraction coupling

  1. powerstoke of myosin heads moving actin
  2. myosin unbinding from actin
  3. active transport of Ca2+ into the sarcoplasmic reticulum
  4. active transport of Na+ and K+ for depolarization (action potentials)

ATP is the only energy source that can be used so muscles have a few metabolic pathways for making ATP

Muscle metabolism

ATP is the only energy source that can be used so muscles use 3 metabolic pathways for making ATP

  • Aerobic: oxidative phosphoralation
  • anaerobic: glycolysis followed by lactate build up
  • alternative: creatine Phosphate

Creatine phosepate

is stored in muscle fibers

provides a rapid source of energy for 10-15 sec of contraction

transfers energy and a phosphate to ADP forming ATP. its essentially holding onto and immeditae source of phosphate bonds which can provide that phosphate ATP when needed. it is a very fast source of energy

Creatine kinase catalyzes the transfer of a posphase group from CP to ADP to rapidly yield ATP

Glycolosis- anaerobic

glucose is broken down into pyruvate and can then enter into aerobic respiration if oxygen is available if oxygen is not available then pyruvate will be broken down into lactic acid. we get a few ATP from Glycolosis however we get even more ATP from Aerobic respiration but if oxygen is not available that couple of ATP can help muscle cell function. muscle cells also store lots of glycogen.

glucose is broken down to pyruvic acid and produces 2ATP

in the absence of O2 pyruvic acid is converted to lactic acid (the acid can build up)

produces minimal amounts of ATP but occurs quickly

Provides 30-60 seconds of high level activity

This will be the primary source provides ATP for the contraction and for the pumps required

Oxidative phosphorylation - Aerobic respiration

-occurs in the mitochondria

-main soucrce when CO2 is present

-fueled by glycogen stores and glucose and fatty acids delivered by the blood this can provide hours of muscle contraction for prolonged moderate activity it is slower becuase it requires the delivery of oxygen and glucose

muscle fatigue

fatgue- decline in muscle tension as a result of pervious activity

muscles are unable to contract despite being stimulated

-results from a deficit of ATP (not a total absence)

-anaerobic respiration becomes less efficient as lactic acid accumulates a pH drops in the muscle fiber

-muscle fibers lose K+ as the Na-K pump is unable to restore ion balance since it requires ATP

-neuromuscular fatigue is caused by a shortage of neurotransmitters at athe NMJ

Muscle fatigue will happen if muscles are depleted of ATP aerobic resporation will be less efficient as lactic acid builds up and the pH drops in the muscle fiber they will also lose potassium and sodium as the sodium potassium pump is unable to restore the ion balance

Oxygen debt- the amount of extra oxygen the body must take in to restore muscle chemisty back to resting state

-the liver converts lactic acid in the blood to pyruvic acid which can be converted to glucose or enter aerobic respiration now that O2 is Available

-Glycogen stores are replenished in muscles and liver

-creatine is rephosporylated into creatine phosphate and stored in muscles

-o2 rebinds to myoglobin

Muscle fiber types

muscle fibers differ in their methods of metabolism based on

-pathways they used to produce ATP

  • Oxidative or glycolytic
  • affects duration of muscle contraction

-How quickly their ATPases work

  • fast or slow ATPases enzymes
  • affects the speed (velocity ) of contraction

3types

-slow oxidative (type 1)

slow contraction s but most resistant to fatigue

good for endurance and continuous contraction

better equiped fro oxidative phosphoralation

  • numerous mitochondria and rich supply of capillaries
  • small in diameter

high myoglobin content

-slow myosin ATPase activity

-fast Oxidative(type IIa)

fast contractions but resistant to fatigue

-also equiped for oxidative phosphorylation

-fast myosin ATPase activity

-fast Glycolytic (type IIx)

fast contractions but fatigue qiuckly

good for power and speed for shor durations

  • high glycogen reserves and relies mainly on glycolysis
  • fatigue quickly due to lactic acid build up
  • large fibers generate more force but poor nutrient diffusion
  • light in color due to reduced myoglobin
  • fewer capillaries and mitochondria

Neuromuscular Junction

The surface of the muscle has ligand gated sodium channels and on the neuron we have the calcium voltage gated channels. Calcium and sodium are prodominantly abundant on the outside of these cells how ever they want to get in but cannot due to the voltage gated channels. At rest the inside of the neuron is negative with respect to the outside but when an action potential arrives at the end builds it will change the inside to be more positive this change in charge will then open the calcium voltage gated channels allowing calcium ions to come inside this is called calcium influx. This is going to cause the end bulbs to become even more positive causing the inner vesicles to release acytelcholine into the synaptic cleft (neuromuscular Junction) the acetylcholine will bind to the ligand gated sodium channel causing the channels to open up and allow sodium into the muscle this will cause an action potential in the muscle itself causing muscle contraction. After contraction acetylcholine will detach from the ligand gated sodium channels and move back into the synaptic cleft sodium will move back out of the muscle acetylcholinesterase will breakdown acetylcholine into choline and acetate. Choline and acetylcoA can bind together to make new acetylcholine and then the process repeats