Craniofacial Histology - Muscle Physiology

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Characteristics of Muscle

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Responsive (excitable):capable of response to chem signals, electrical signals, and stretch
Conductive:local electrical change in a cell triggers a wave of excitation that travels along the cell
Contractile: cells shorten when stimulated by converting the chemical energy of ATP into mechanical energy
Extensible:cells are capable of being stretched
Elastic: cells return to original resting length after being stretched
General Characteristics: muscle tissue is composed of CT, BV, nerves, lymphatics and muscle cells.

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Types of Muscle Tissue

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Striated Muscle (cytoplasm has cross striations)
Striated Skeletal Muscle (voluntary muscle)
Striated Cardiac Muscle
Smooth Muscle (cytoplasm without cross striations)

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Skeletal Muscle

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Skeletal Muscle is voluntary striated muscle attached to bones
Voluntary means under conscious control
Skeletal muscle fibers = myofibers = muscle cells
Skeletal muscle fibers are as long as the whole muscle
Skeletal muscle is a striated muscle.
striated muscle exhibits alternating light and dark transverse bands or cross striations in the cytoplasm that are from the highly organized contractile proteins of the cytoskeleton

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Series Elastic Components of the Musculoskeletal System

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CT layers of skeletal muscle tissue are continuous with the CT of bones: epimysium, perimysium, endomysium, tendon, periosteum
CT is extensible and elastic which means that it stretches under tension and recoils when released
Series-elastic Components are all of the interconnected CT in muscle that are attached to the bone membranes, help return muscles to their resting lengths, adds significantly to power output and efficiency of muscles, moderate elastic to absorb shock (too much would waste energy)

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Skeletal Muscle Fibers

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Sarcolemma is the specialized plasma mem of muscle cells, is polarized at rest and can be depolarized by Ach released by motor neurons, tubular infoldings of the plasma membrane are called transverse tubules (T-tubules) that penetrate into the cell and carry the electrochemical current into the cell
Sarcoplasm is the specialized cytoplasm of muscle cells.
sarcoplasm is filled with highly organized myofibrils (bundles of parallel protein microfilaments of actin and myosin) and glycogen for stored energy and myoglobin for storing O2
Sarcoplasmic reticulum is the specialized ER of muscle cells. is a series of interconnected tubules connected to dilated, storage sacs called terminal cisternae that store calcium ions (Ca++)

Front 6

What type of muscle is this?

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Skeletal muscle.

Front 7

Syncytial Skeletal Muscle Development

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Each muscle fiber has multiple nuclei flattened against the inside of sarcolemma. multiple nuclei are from the fusion of multiple myoblasts (derived from a condensation and of mesenchymal cells) during development forming a syncytium. a syncytium is a multinucleated mass of cytoplasm that is not separated into individual cells. unfused satellite cells outside the sarcolemma between muscle fibers can multiply to produce a small number of new myofibers or add nuclei to existing myofibers

Front 8

What is shown.

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Sarcomere: fxl unit of muscle
Name the Z, H, M I regions

Front 9

Muscle Filaments of the Sarcomere

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Sarcomeres are the functional units of muscle
Thin filaments are actin
Thick filaments are myosin
Elastic filaments are titin
Ahem, I Zee!

Front 10

Regions of the Sarcomere

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A Band extends from myosin tip to myosin tip. stands for anisotropic which is a term for the way polarized light passes through the thick filaments giving it a dark appearance.
H Band is the central region of the A band and is a region of myosin without actin.stands for Helle (German for bright).
M Line is a disk of protein that anchors the myosin filaments. stands for Mittel (German for middle)
I Band is the thin filament region stands for Isotropic: polarized light passes easily through it giving it a light appearance
Z Line is a disc of alpha actinin protein that anchors titin and actin filaments stands for Zwischen (German for between)

Front 11

Contractile Proteins and Regulatory Proteins

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Actin and Myosin are contractile proteins, movements contract the cell
Troponin and Tropomyosin are regulatory proteins that act like a switch that starts and stops contraction of muscle cells
The regulatory proteins are dependent upon Ca++

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Thick Filaments

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Thick filaments are made of hundreds of myosin molecules
Myosin is composed of two entwined polypeptides (each shaped like a golf club with a spiral handle) Myosin is arranged in bundles with the heads directed outward in a spiral array around the bundled tails. H Zone is the region with no heads that contains the M line

Front 13

Thin Filaments

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Thin filaments are composed of two strands of fibrous actin composed of 6 or 7 globular actin (G actin) subunits each with an active site.
Tropomyosin molecules cover and block the active sites of 6 or 7 G actin subunits.
One calcium-binding troponin molecule is attached to each tropomyosin molecule

Front 14

Elastic Filaments

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Huge springy protein called Titin is an elastic filament that connects the Z disc to the M line, passes through the bundles of thick filaments
Fxns of Titin: keeps thick and thin filaments aligned with each other, resist overstretching, help the cell recoil to its resting length (provides elasticity)

Front 15

Relaxed versus Contracted Sarcomere

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Muscle cells shorten bc pulling Z discs closer together.
Notice that filament overlap changes, but neither thick nor thick filaments change length during shortening.
During contraction:
A band length stays the same
H zone shrinks
I band shrinks
During relaxation, compressed titin rebounds and pushes Z disks apart to the resting length

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Innervation of Skeletal Muscle

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will not contract unless it is stimulated by a nerve cell (neuron). paralysis is a loss of fxnl innervation and results in the atrophy of the muscle
Cell bodies of somatic motor neurons are in the brainstem and spinal cord
Axons of motor neurons are branched. each axon can branch a few times (3-6) or many times (over 200) Each axon branch of a somatic motor neuron contacts one muscle fiber, axons = nerve fibers. A motor unit is a motor neuron and all the muscle fibers it innervates

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Motor Units

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Muscle cells of a Motor Unit are dispersed throughout a muscle. provides ability to sustain long-term contraction as motor units take turns resting
Small Motor Units provide Fine Control. small motor units contain as few as 3-6 muscle fibers per nerve fiber
example: eye muscles
Large Motor Units are for Strength. large motor units have as many as 1000 muscle fibers per nerve fiber
example: gastrocnemius muscle

Front 18

Neuromuscular Junction

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Synapse is the fxnl connection bw a nerve cell and its target cell. NMJ is a synapse between a nerve fiber and a muscle cell. Components of the NMJ: terminal boutton (synaptic knob, terminal button, axonal swelling, synaptic bulb, end bulb) is the swollen end of nerve fiber and contains vesicles of the neurotransmitter (ACh), motor end plate is the specialized region of muscle cell membrane under the terminal boutton, end plate membrane has ACh receptors on jxnl folds which bind ACh released from the nerve acetylcholinesterase is an enzyme in the basal lamina in the synaptic cleft that breaks down ACh and causes relaxation synaptic cleft is the gap bw the nerve and muscle cells Schwann cells cover the axon and the NMJ

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Muscle and Nerve Electrochemical Communication

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At rest, muscle cell and nerve cell membranes are polarized (charged). Changes in charge are relayed from one cell to another. Membrane polarity or charge is measured in units of volts muscle cell membrane = .06 volts or 60 millivolts (mV)
Difference in charge across the membrane is called the membrane potential. Resting Membrane Potential is est. by a Na+/K+ membrane pump that results in high [Na+] outside of cell and high [K+] and anions inside of cell resulting in a slightly negative voltage inside the cell (-60 mV).
Sarcolemma depolarizes in response to motor neuron stimulation from release of ACh. Voltage change spreads across the membrane as an action potential

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Sodium-Potassium Exchange
Function of the Neuromuscular Junction

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Resting mem pot of -60 mV is est by the Na+/K+ ATPase pump and non-gated K+ channels (leak channels)

Opening of Na+ channels is triggered by ACh and allows Na+ to rush in depolarizing the membrane. Mem depolarization triggers the opening of K+ channels and closing of Na+ channels. K+ leaves the cell through the open channels and the Na+/K+ pump works to drop the mem pot back to resting levels.

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Four actions are involved in Muscle Contraction and Muscle Relaxation:

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Excitation: action potentials in the nerve lead to formation of action potentials in a muscle fiber
Excitation-Contraction Coupling: action potentials on the sarcolemma activate myofilaments
Contraction: shortening of a muscle fiber or at least the formation of tension
Relaxation: return of a muscle fiber to its resting length

Front 22

Excitation

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Nerve signal stimulates voltage-gated Ca channels at the synaptic knob resulting in exocytosis of synaptic vesicles containing Ach. ACh is released into the synaptic cleft.
ACh released from the motor neuron binds to ACh receptors in the sarcolemma, causes it to open a channel for Na+ and K+. A lot of Na+ rushes in and a little K+ rushes out resulting in a membrane voltage change called the End-Plate Potential. The voltage changes from negative to positive.
The End-Plate Potential (voltage change in the motor end-plate membrane) opens nearby voltage-gated Na+ and K+ channels in sarcolemma producing a depolarization that spreads across the sarcolemma. The spreading depolarization is the Muscle Action Potential.

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Excitation-Contraction Coupling

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AP (mem depolarization) spreads over the sarcolemma and down T tubules.T tubule mem depolarization triggers the opening of voltage-gated Ca channels in the SR allowing release of Ca++ from the SR into the sarcoplasm.
Ca++ released by the SR binds to troponin. Troponin-tropomyosin complex changes shape and exposes active sites on actin.

Front 24

Contraction

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Myosin ATPase in myosin head hydrolyzes an ATP molecule.
Energy from the ATP “cocks” the myosin head in a high energy extended position. Myosin head binds to an exposed active site on actin forming a cross-bridge.
Power Stroke:myosin head releasesthe ADP and Pi as it flexes pulling the thin filament along. If ATP is available, ATP binds to the myosin head and it releases the thin filament and extends. It will attach to a new active site further down the thin filament if Ca++ is still available and bound to troponin. to prevent slippage, at any given moment, half of the heads are bound to a thin filament, while the other half of the heads are re-setting.

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Relaxation

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Nerve stim ceases and acetylcholinesterase breaks down ACh. ACh no longer bound to receptors so sarcolemma repolarizes.
Active transport (using ATP) by integral membrane protein pumps in the SR removes Ca++ from the sarcoplasm and stores it in the SR where it is bound to the protein calsequestrin. ATP is needed for muscle relaxation as well as muscle contraction.
Loss of Ca++ from the sarcoplasm results in troponin-tropomyosin complex moving over the actin active sites which stops formation of cross bridges and prevents muscle tension.Muscle fiber returns to its resting length due to elastic rebound of titin and the series-elastic components or contraction of antagonistic muscles.

Front 26

Rigor Mortis

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Stiffening of the body beginning 3 -4 hrs after death peaks at 12 hrs after death then diminishes over next 48-60 hrs.
Deteriorating SR releases Ca. Ca activates actin-myosin cross bridging. ATP is no longer produced after death and without any new ATP, the myosin head remains bound to the actin (does not release). Actin and Myosin fibers remain bound until myofilaments decay.

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Neuromuscular Toxins and Paralysis

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Atropine: antidote that works by blocking ACh receptors
Tetanus: or lockjaw is a spastic paralysis caused by a toxin of the soil bacterium Clostridium tetani. the toxin blocks glycine, an inhibitor normally produced by the spinal cord that prevents overstimulation of muscles.
Clostridium botulinum: is a related soil bacterium that produces botulinum toxin that blocks ACh release from motor neurons.
Curare: causes flaccid paralysis with limp muscles that are unable to contract.A South American plant toxin used by indigenous people to make poison darts.Binds to ACh receptors without activating them.Used as a muscle relaxant for surgery, but can cause respiratory arrest.
Black Widow Spider venom: causes massive release of ACh that leads to uncontrolled muscle spasms.
Tetrodotoxin (TTX): blocks voltage-gated Na+ channels.
TTX blocks Na movement into the neuron and the AP along the nerve membrane ceases.  A single milligram or less of TTX - an amount that can be placed on the head of a pin, is enough to kill an adult. 10-100 times more toxic than black widow spider venom

Front 28

Myasthenia Gravis

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Autoimmune disease where antibodies bind to ACh receptors Skeletal muscle cells become progressively less sensitive to ACh Symptoms include: drooping eyelids and double vision, difficulty swallowing, weakness of the limbs, respiratory failure. Disease affects mostly women between ages of 20 and 40. Treated with cholinesterase inhibitors, thymus removal or immunosuppressive agents

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Length-Tension Relationship

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Overly contracted muscle cells develop a weak contraction bc the thick filaments are already close to the Z discs and further contraction results in the ends of the thick filaments butting up against the Z disc.Also develop a weak contraction bc there is too little overlap of thin and thick filaments which does not allow for very many cross bridges too form.
Optimum resting length produces greatest force when muscle contracts

Front 30

Muscle Twitch

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Threshold is the min. V necessary to produce an AP in a muscle cell.a single brief stimulus at threshold voltage produces a quick cycle of contraction and relaxation called a twitch that lasts less than 1/10 second.A single twitch contraction is not strong enough to do any useful work.

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Stimulus Frequency and Muscle Tension of Twitch & Treppe

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Twitch: at low freq (up to 10 stimuli/sec) each stimulus produces an identical twitch with complete relaxation in between.
Treppe: at moderate freq (between 10-20 stimuli/sec) the muscle relaxes completely bw twitches, but the tension increases with each twitch because Ca is not completely reabsorbed into the SR. Also, the heat produced by muscle contraction increases myosin ATPase efficiency (as in warm-up exercises).

Front 32

Stimulus Frequency and Muscle Tension
Icomplete tetanus & Complete tetanus

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Incomplete Tetanus results from higher freq stimulation (20-40 stimuli/second) and gradually generates stronger, sustained contractions.each stimulus arrives before the previous one recovers, this is called temporal summation bc it results from the timing of the stimuli.
Complete Tetanus usually results from an artificially high stimulation freq (40-50 stimuli/second), muscle has no time to relax bw stimulations, twitches fuse into a smooth, prolonged contraction, rarely occurs in the body under natural conditions

Front 33

Asynchronous Contraction

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The reason for the smoothness of muscle contraction during muscle tetany is that the motor units function asynchronously. throughout an actively contracting muscle, some motor units are contracting as others relax.
the muscle does not lose tension as motor units take turns developing tension within the muscle.

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Energy for Muscle Contraction

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ATP is the ONLY source of energy for muscle contraction. produced by: aerobic respiration, produces about 36 ATP per glucose molecule, requires continuous O2 supply, produces H2O and CO2 as waste, anaerobic fermentation
produces only 2 ATP per glucose molecule, occurs without O2 and produces irritating lactic acid as waste

Front 35

Phosphagen Enzyme System

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Myokinase and Creatine Kinase generate ATP in the absence of O2.
Myokinase uses Pi from ADP.
Creatine Kinase uses Pi from creatine phosphate.

Front 36

Sources of ATP During Intense Exercise

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Immediate Energy: ~10 Sec supply of ATP from: Aerobic metabolism using O2 released from myoglobin in muscle cells. Phosphagen System of enzymes that transfers Pi to ADP.
Short-Term Energy: ~30-40 second supply of ATP
Glycogen-Lactic Acid System uses stored glycogen and anaerobic metabolism producing lactic acid.
Long-Term Energy: After ~40 seconds if the respiratory and cardiovascular systems are fxn well, they can catch up to O2 demand for aerobic respiration and supply more than 90% of ATP during sustained exercise.

Front 37

Oxygen Debt

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The need to breath heavily after strenuous exercise is to provide maximal oxygen for: replacing O2 reserves in myoglobin and hemoglobin, replenishing the phosphagen system, converting lactic acid back into glucose in kidneys and liver, serving the elevated metabolic rate that occurs as long as the body temperature remains elevated from exercise

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Fast Fibers, Slow Fibers, and Intermediate Fibers

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fast fibers: pale and often called white muscles. Chicken breasts contain "white meat" because chickens use their wings only for brief intervals, as when fleeing from a predator, and the power for flight comes from fast fibers in their breast muscles.
Slow Fibers: The extensive BV and myoglobin give these fibers a reddish color; muscles dominated are therefore known as red muscles. Chickens walk around all day, and the movements are performed by the slow fibers in the "dark meat" of their legs.
Most human muscles contain a mixture of fiber types and appear pink. However, there are no slow fibers in muscles of the eye or hand, where swift but brief contractions are required. Many back and calf muscles are dominated by slow fibers; these muscles contract almost continuously to maintain an upright posture.
Intermediate fibers: have charac of both fast twitch and slow twitch fibers.
The % of fast versus slow fibers in each muscle is genetically determined, but the proportion of intermediate fibers can increase as a result of athletic training.

Front 39

Red?
Pink?
White?

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REd = Type I - slow oxid. red fibers
WHite = Type IIa - fast oxid. white fibers
Pink = fast glycolytic intermediate fibers

Front 40

Fast Fibers

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Most of the skeletal muscle fibers in the body are bc they can contract in 0.01 sec or less after stimulation. large in diam; contain densely packed mofibrils, large glycogen reserves, and relatively few mitochondria. The tension produced by a muscle fiber is directly proportional to the number of sarcomeres, so muscles dominated by fast fibers produce powerful contractions. However, fatigue rapidly bc their contractions use ATP in massive amounts, so prolonged activity is supported primarily by anaerobic metabolism. Several other names are used to refer to these muscle fibers, including white muscle fibers, fast-twitch glycolytic fibers, and Type II-A fibers.

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Slow Fibers

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Slow fibers are only about half the diameter of fast fibers and take three times as long to contract after stimulation. Slow fibers are specialized to enable them to continue contracting for extended periods, long after a fast muscle would have become fatigued. The most important specializations improve mitochondrial performance. Slow muscle tissue contains a more extensive network of capillaries than is typical of fast muscle tissue and so has a dramatically higher oxygen supply. In addition, slow fibers contain the red pigment myoglobin. This globular protein is structurally related to hemoglobin, the oxygen-carrying pigment in blood. Both myoglobin and hemoglobin are red pigments that reversibly bind oxygen molecules. Although other muscle fiber types contain small amounts of myoglobin, it is most abundant in slow fibers. As a result, resting slow fibers contain substantial oxygen reserves that can be mobilized during a contraction. Because slow fibers have both an extensive capillary supply and a high concentration of myoglobin, skeletal muscles dominated by slow fibers are dark red. They are also known as red muscle fibers, slow-twitch oxidative fibers, and Type I fibers.
With oxygen reserves and a more efficient blood supply, the mitochondria of slow fibers can contribute more ATP during contraction. Thus, slow fibers are less dependent on anaerobic metabolism than are fast fibers. Some of the mitochondrial energy production involves the breakdown of stored lipids rather than glycogen, so glycogen reserves of slow fibers are smaller than those of fast fibers. Slow fibers also contain more mitochondria than do fast fibers.

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Intermediate Fibers

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properties intermediate bw those of fast fibers and slow fibers. most closely resemble fast fibers, contain little myoglobin and are relatively pale. They have a more extensive capillary network around them, however, and are more resistant to fatigue than are fast fibers. Intermediate fibers are also known as fast-twitch oxidative fibers and Type II-B fibers.
the proportion can change with physical conditioning. For example, if a muscle is used repeatedly for endurance events, some of the fast fibers will develop the appearance and fxnl capabilities of intermediate fibers. The muscle as a whole will thus become more resistant to fatigue.

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Cardiac Muscle

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shorter and thicker than skeletal muscle cells, are also branched and linked to each other at intercalated discs. gap jxns synchronize muscle contractions,desmosomes keep the cells from pulling apart, Large T tubules facilitate absorption of Ca++ from extracellular fluid, damaged cells are repaired by fibrosis, not mitosis, Autorhythmic due to pacemaker cells, Uses aerobic respiration almost exclusively, very vulnerable to interruptions in oxygen supply, use fatty acids for primary energy storage, large, abundant mitochondria resist fatigue

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Smooth Muscle

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Fusiform cells with one nucleus, no visible striations, sarcomeres or Z discs. thin filaments attach to dense bodies scattered throughout sarcoplasm and attached to the sarcolemma. thick filaments are suspended bw the thin filaments. gap jxns spread depolarization from cell to cell
Ca for contractions comes from poorly developed SR and from extracellular fluid. If present, nerve supply is autonomic releases either ACh or norepi. different effects in different locations

Front 45

Smooth Muscle Contraction

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stimulated by NTs, hormones, high CO2, low O2, low pH, stretch. Stimulated, absorb extracellular Ca++ through channels or by release of Ca from SR. The free Ca binds to a special Ca binding protein called Calmodulin. Calcium-calmodulin activates myosin light chain kinase (MLCK), an enzyme that uses ATP to phosphorylate the myosin light chains (MLC) in the myosin head.Myosin light chains are regulatory subunits found on the myosin heads. The activated myosin heads form cross bridges with actin filaments. The power stroke occurs when a 2nd ATP is hydrolyzed by myosin ATPase. Ratcheting of the myosin head causing contraction. Thin filaments pull on intermediate filaments attached to dense bodies on the plasma membrane which shortens the entire cell in a twisting fashion. Contraction and relaxation is very slow in comparison to striated muscle:
the myosin ATPase enzyme and the pumps that remove Ca++ are slow. More efficient than skeletal muscle: smooth muscle uses 300 times less ATP to maintain a given tension than skeletal muscle

Front 46

Responses of Smooth Muscle to Stretch

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Stretch opens mxl-gated Ca channels causing muscle contraction. example: food in the intestines brings on peristalsis. Stress-relaxation response necessary for hollow organs that gradually fill (urinary bladder).when stretched gently, tissue briefly contracts then relaxes. Contracts forcefully when greatly stretched.Contraction force matches degree of stretch