Muscle Physiology:
09.20.01
3 Types:
1. Skeletal:
-striations
-multi-nucleated
-under voluntary control (except for the diaphragm)
-each one does not communicate with the next
-always need nerve input
2. Cardiac:
-striated
-one or two nuclei
-not as long as skeletal muscle
-more net like
-communicate with each other
-divide and recombine to form anatomical and functional syncytium
-not controlled by nerve input, but rather are driven by a pacemaker
-called the SA node and is modified to fire spontaneously
-the nerve supply works as a modulator
-not under voluntary control
3. Smooth:
-no striation
-very small (the smallest)
-usually only one nucleus
-not under voluntary control except for a few cases
-two types
-those connected with pacemakers (like cardiac)
-those like skeletal muscles
Organizations of Skeletal Muscles:
- occur in bundles
- surrounded by epimyosin (tough white outer coating)
- fascicles surrounded by perimyosin
- ex: nerve cell is made of nerve fibers all surrounded by tough membrane
called the endomyosin
- cell includes: mitochondria, many nuclei, very orderly fibril arrangement of
myofibrils (1000 to 10000)
- ends of the cells bunch together and taper off to form the tendon
- causes the spindle shape
- allows for insertion into the bone
Why are they multi-nucleated?
- muscle cells form as a result of the fusion of myoblasts or myocytes
The Myofibril:
- reason for the muscle’s striation
- made up of two types of protein
1. actin – the thin filament
2. myosin – the thick filament
- interdigitated/interlocked with each other
- each actin filament is attached to a Z-membrane or Z-line
- between two Z-lines is the smallest contractile unit called the sarcomere
- actin by itself on either side of the Z-line looks light and is called the I band
(isotropic)
- myosin and actin over lap giving the dark band or A band (anisotropic)
- H zone – just the myosin
- M line – dark line in the middle of H-zone–represents myosin’s thicker center
- sarco-tubular system:
- surrounds the micro tubules
- invagination of sarcolemma that goes deep in and surrounds the myofibrils
- filled with extra cellular fluid
- “swiss cheese” – sarcoplasmic reticulum
- thickens when close to the t-tubules
- transverse tubules or t-tubules
- triad: two sarcoplasmic reticulums and the t-tubules between them
- terminal cisternia
- filled with a protein with the ability to hold calcium
- called sequestrin
- has many calcium pumps that can concentrate 1:10000
- calcium is the trigger for contraction and it will be removed from the
outside entirely
Contraction:
- requires activation or nerve input
- AP comes down the nerve axon (see notes)
- Na and Ca enter the muscle cell giving an EPP that becomes and AP
- slower conduction than nerves
- much wider AP than nerves
- AP invades the entire sarcolemma in all directions as with as the t-tubules
- causes Ca2+ to b e released and triggers contraction
09.25.01
EEP to the AP
- The AP enters the t-tubules which causes the release of Ca at the triad called the calcium pulse.
- The calcium puffs into the cytoplasm around the contractile units (10-7 to 2 x 10-5 rise)
- ended by the pump removing the calcium
Mechanisms for Contraction
- calcium activates the actin and the myosin and actin slide over each other (sliding
filament theory)
-myosin has projections moving away from the center called the cross bridges
-they latch on to the actin and pull causing two Z-lines to move in
-1000’s in a whole muscle fiber causing the whole muscle to shorten
Myosin
-comprised of 6 polypeptides
-2 of the 6 are of large molecular weight called the heavy chain myosin molecules
-the other four are called light chain myosin
-heavy chains wrap around each other forming a helix and the end polymerizes to form the gobular head
-has two flex points, one at the head and one further down the tail called hinges
-100’s for each myosin filament
Actin
-3 protein types
-F-actin: 2 strands of beads in a double helix
-Beads are made of G actin and have an active site at regular intervals
-Believed to be attracted to the cross bridges
- tropomyosin: has two long thing strands forming a helix (rope)
-at rest, they block the active sites on G actin
- troponin: gobular molecule attached to tropomyosin
-arranged at predestinated/regular intervals near the active site to help block site
Contraction
-when calcium activates the contractile mechanism the two filaments slide over each other
-called the walk along, ratchet, or rowing boat theory
-“oars” are the cross bridges when the active sites are exposed
-pull the thin filaments inward
-each pull is called a power stroke
-energy is ready and waiting in the head (the ATP is already split)
-Ca attachment to the troponin causes a structural change and reveals the active site
-Head immediately attaches, tilts and drags the actin with it (releasing the ADP)
-Opens up a site for ATP to attach causing the cross bridges to detach
-ATP is spit again into ADP and energy and the cross bridge goes back to the original resting situation
-ATP must be continually manufactured from phosphocreatin
-Muscle can utilize free fatty acids and glucose for energy
-Not very good machine thermodynamically (produces more heat than work)
-25 to 50% of energy produced goes to work, the rest to manufacture ATP or heat (~70% lost as heat)
Rigor Mortis
-stiffening at death: muscles enter a continual contraction
- due to the facts that:
-ATP is no longer being generated
-Ca is no longer being pumped out of the muscle
-CA is still able to enter (diffuse) from the outside in
-Skeletal muscles cannon contract spontaneously
-there must be a motor nerve from the spinal cord to muscle uninterrupted
-motor unit: a single motor neuron and all the muscles it supplies
-Muscle tone:
-Result of nerve input
-There is a structure in each muscle that measures the amount of contraction in it and keeps it at a certain tone
09.27.01
-Muscle twitch:
-Contraction as a result of a single AP
-Occurs when the AP is almost over
-Has no refractory period
-Can build up to a contraction via summation
-Tetanize:
-Stimulate at a rapid frequency
-Twitches summate until reaching a constant contraction
-Complete tetanus: the muscle never has time to relax
-Adds smoothly
-Incomplete tetanus: similar to complete but you can see the beginning of relaxation (lower frequency of stimulation)
-Hz – hertz = pulse/second
-When a resting muscle is stimulated the first response is small the second higher, higher, higher and so forth on until it stabilizes at some height
-Called the stair case effect (or treppe)
-Due to the availability of calcium
Types of Contraction:
1. isometric: stays the same length but is still contracting
- other components in a series with muscle fibers (tendons, etc) called the series
elastic components (SE) stretch when the muscle contract so that the actual
muscle structure stays the same length
2. isotonic: muscle shortens while contraction but keeps the same tension
-strength contraction is dependant on the number of cross bridges involved
-at C: all the cross bridges are engaged
-at B: the tips of the actin over lap and you loose some cross bridge engagement as some active sites are lost
-at A: point where the muscle is as short as possible and the myosin is touching the Z-line
-at D: complete relaxation
-Load velocity: the higher the load on the muscle, the slower the contraction
Muscle Energetics (read in BOOK)
-has a big requirement for ATP
-two types of contraction: aerobic and anaerobic
-Tone: oxygen and fatty acids from the blood will produce ATP in the mitochondria
-Glucose form the blood is stored as glycogen (which requires energy)
-Creatin is phosphoralated to creatin-phosphate which is an immediate source of energy
-During moderate activity: glycogen is converted back to glucose which is converted into pyruvate acid which enters the mitochondria and can produce ATP
-During severe exercise: there is no O2 causing an oxygen debt which must be repaid
-Depends on the conversion of glycogen to glucose to produce ATP as well as the ATP from creatin
-Causes lactic acid to be produced which is then sent to the blood stream and may cause acidosis
Muscle Fatigue- due to the fact that:
1. the store of glycogen is depleted
2. ATP is depleted
3. O2 is depleted
4. creatin-phosphate is depleted
5. acetyl choline is depleted
Muscle Types:
1. Fast (white): larger in size, pale, fatigues easily and quickly, requires a higher amount of ATP, short duration of contraction (5 to 7 ms)
2. slow (red): smaller, red because of large amount of myloglobin-has the ability to carry O2 like hemoglobin and many, many blood capillaries, involved I contraction against gravity, can twitch up to 100 ms
3. intermediate: reddish, but otherwise resembles fast muscle, more resistant to fatigue than white muscle
09.28.01
Abnormalities in Function:
1. hypertrophy-the result of exercise
-the muscle increases in size and the amount of cretin phosphate and ATP and glycogen storage increase
-it is natural growth and will revert to normal when the exercise stops
2. atrophy-2types
-disuse: when a muscle is not used or worked at all it will become very small
-Ex: one month in a cast and muscle size is cut by ½
-Will build back up with use
-denervation: when the skeletal muscle looses its nerve supply
-Will decrease in size because it is inactive
-Degeneration and atrophy can continue for up to three years
-If the nerve comes back within three or four months, the muscle will fully revive (after three or four years the muscle is nothing but fat and tissue)
-If the nerve does not come back then there is a decrease n size and a shortening unless passive stretching is applied every day
-Can contort the body as it shortens (POLIO)
-Muscle becomes super sensitive
-Due to acetyl choline receptors spreading to cover the whole muscle
-Similar to the embryonic muscle
-Have 50% more receptors than needed
-When the muscle gets a nerve, the other receptors degenerate
-Muscle wants activity and so twitches
-If a nerve grows back to a super sensitive muscle, the extra receptors will disappear
-Trophic influence of muscle and nerve
-Need each other to survive
-Experiment: switched nerves for the slow and fast muscles and they started to behave like each other
-Everything changes, including function and appearance
-Fasciculation: a state of muscle contraction
-Other wise known as a twitch
-Fibrillation: very high frequency contraction of muscle
-In a bundle, each cell will not contract together
-Like a balloon filled with worms-each is quivering on its own
-Can result from supersensitivity, denervation, and a serge of many Aps
-Can be recorded on an electromyography-diagnostic tool used to record muscle activity from above the skin
-Blood flow and ascemic pain:
-Exercise causes fatigue and pain due to the activation of pain receptors in the muscle because of lactic acid, lack of O2, etc
-Ascemia is the lack of oxygen
-Due to the fact that contraction has squeezed out all of the blood supply
-Aging: atrophy due to inactivity
-Can be prevented with exercise
Cardiac Muscle:
-3 types:
-atrial (top)
-ventricular (bottom)
-excitatory-conductive
-specialized for conduction of electrical impulses
-also called the pacemaker
-found at the SA and AV nodes (where impulses are generated)
-conductive-goes into which membrane that separates the left and right ventricles call the Bundle of Hiss
-very little contractile ability -designed to generate or conduct impulses
-rhythmically discharges
-very fast conduction
-Anatomy:
-Striated (exactly the same as skeletal muscle)
-Each cell cannot independently contract (syncytium)
-The cells divide, branch and rejoin to form a lattice
-Site of connection is called the intercalated disk
-It is a form of electrical synapse called a gap junction
-About 400x more conducive to electrical charges than the membrane and allows for impulses to go in both directions
-If you stimulate on fiber the entire muscle contracts
-Called a functional syncytium
-But the stimulation must be above the threshold
10.02.01
anatomical syncytium is when they are physically connected
functional syncytium is when if stimulated they all contract
RMP (resting membrane potential)
-variable at the ventricle and atrial muscle and nodes
--85 to –90 at the A and V
--55 to –60 at SA and AV nodes
--95 to –100 at the conductive tissues (such as the bundle of hiss)
-gives a plateau action potential
-the atrium’s is shorter than the ventricles
-review the ionic basis (notes 1)
-Ca2+ channels open and K+ channels close
-the refractory period is very long (absolute refractory period)
-up to 300 ms (absolute
-relative is short (only 50 ms)
-contraction is during the AP
-makes it nearly impossible to tetanize cardiac muscle
-PQRST
-When the collective electrical signal of the heart is recorded via electrodes on the chest
-P is the contraction of the atrium
-QRS is the contraction of the ventricle
-T is the relaxation of the ventricle
-Contraction: almost exactly the same as skeletal muscles
-Differences?
-CA2+ is required but the source is different due to the variation in structure
-SR system is not very well developed and cannot store Ca2+
-The t-tubules are much better developed (5x thicker)
-Filled with mucopolysacchrides that can hold Ca2+
-Most Ca2+ comes from the outside not the triad
-The Ca2+ is pumped back into the t-tubules and is sequestered by the mitochondria
-The AV muscle contracts more forcefully when stretched
-In the ventricle: the more the amount of filling (blood) the more it will stretch
-Called the end diastolic volume: the amount of blood is responsible for the force of contraction
-Beyond a certain limit or amount the muscle looses ability to contract called Frank-Starling Law
-The more stretch the more contraction until a point beyond which causes the opposite effect
-Main cause of congestive heart failure
-The main energy supply is the metabolism of fatty acids an to a lesser extent sugars (glucose and lactose)
-Specialized Tissues:
-Pacemaker: provides a rhythmic AP
-RMP is unstable (-55 to –60) and so give spontaneous activity
-Cells have pacemaker potential and pre potential
-Du to sodium leakage into the cell because of its low negativity and a decrease of K permeability
-Located mainly in the SA and AV node, but there are latent scattered pacemaker cells
-If the need arises they assume the pacemaker’s activity
-3 pathways that connect the SA and AV nodes
-they are a like of muscle cells that are specialized for conducting impulses
-the fibers from the AV node go from the septum and ventricular walls
-Nerve supply
-Colenergic and adrenergic
-AV and SV nodes function as modulators
-Colenergic impute from the vegas modulates the rate of fire and if you stimulate the vegas the heart rate drops
-Adrenergic innervation supplies mainly the ventricle
-If NE is injected into the ventricle you get a positive ionotropic effect and the heart starts pumping
-The synapses are not well understood but it is believed that it is made of a branch with varicosities (beads) the spray the neurotransmitters into the muscle’s vicinity
-Called en passant (in passing)
-Figure on page 46
Smooth Muscle
-no striations
-no t-tubules
-very small
-found in the GI tract, urogenital tract, vascular structures (excluding the capillaries), bronchi, and capsules of the endochrinic glands
-fusiform (spindle like)
-2 types:
-sheet: one is laying next to the other
-spiral/spring like: chan be tight or loose pitched (lower intestine)
-multi-unit:
-each cell is very independent from each other (like skeletal muscle)
-each has a basement membrane
-nerve driven with no spontaneous activity
-not the usual type of smooth muscle
-found only in the iris of the eye, the pylorector of the hear and the large blood vessels
-unitary (visceral)
-entire muscle reacts as one
-occurs in sheets
-can communicate with each other similar to cardiac muscle
-via gap junctions called nexus
-electrical synapses
-have a functional and anatomical syncytium
-Electrical Functions:
-Difficult to record their RMP (too small)
-Between –50 and –60
-More permeable to sodium
-Contains Cl- pumps (into the cell) that counteract the positivity
-AP do not occur in multiunit types
-Their size is so small they down need AP
-Visceral:
-Has regular AP, but is somewhat slow
-Predominate type
-Plateau AP-serves a similar function as the plateau AP in the heart
-Up to 50 ms long
-Electrical activity has a slow wave rhythm
-Gives an AP when it reaches the top of the wave
-Basis of the AP?
-Many Ca2+ channels
-TTX cannon block the upstroke of the AP because it is not due to Na+
-Innervation?
-Unitary does not require innervation to fire (have the pacemaker cells)
-Nerve supply is only modulators
-There are no real synaptic connections
-Varicosities spray the transmitter and the transmitter enters interstitial fluid between the cells and acts on receptors there
-Can produce either depolarization (EJP) or hyperpolarization (IJP)
-Contractile mechanisms and response:
-Have actin and myosin, but arrangement is different from the cardiac and skeletal muscles
-Many thin filaments
-Very few thick
-No sarcomeres (as presently defined)
-Tropomyosin, but no troponin
-Ca2+ must bind to something else (calmodulin)
-Found in animals, plants, everywhere
- The amount of energy required for smooth muscle contraction is ?less?
-The duration of contraction is much longer
-Actin is attached to dense bodies inside the membrane
-Few myosin but there is enough cross bridges to produce contraction
-2 to 3 kg/cm2
-all Ca2+ for contraction come sin from the outside