MS-1 FUND 1: 11:00-12:00
Thursday, September 11, 2014
Dr. Cotlin
Muscle Tissue
Transcriber: Deepa Etikala
Editor: Naixin Zhang
Page 1 of 5
Abbreviations: SR = Sarcoplasmic Reticulum
Introductory Comments: This is the second hour of Dr. Cotlin’s Muscle Tissue Lecture. The timestamps reflect ECHObased timings.
I.
II.
III.
IV.
V.
Innervation of Skeletal Muscle (slide 42) 00:26
a. Skeletal muscle is voluntary
i. Meaning that every muscle cell will be individually innervated at the motor end plate (also called the
neuromuscular junction)
1. Branched nerve’s processes will attach themselves to every muscle fiber
ii. This happens because there is no communication between these cells
iii. Each cell is individually innervated
b. Neurotransmitter for all skeletal muscle is acetylcholine
c. Region where muscle and nerve meet is called the synaptic cleft
Neuromuscular Junction (slide 43) 01:32
a. Picture on the left
i. Each cell is innervated by axon’s processes
b. Picture on the right
i. Shows myelinated motor neuron
ii. Synapse between nerve muscle cell
1. Synapses don’t have to be between two neurons
2. Synapse indicates the association between the nerve and its effector
a. can be another neuron, muscle, gland, organ, etc.
3. See the buildup of acetylcholine and folded sarcolemma at this region
a. contains several junctions
b. as well as cell adhesion molecules anchoring this structure
4. Will also find high concentration of acetylcholine receptors in the junction
Events Leading to Skeletal Muscle Contraction (slide 44) 02:36
a. Acetylcholine will open sodium channels
b. Sodium will diffuse into the cell and depolarize the membrane
c. There is a very close association between the plasma membrane and the SR
i. Due to this close association, voltage-gated Ca2+ channels are activated in the SR
1. Once open, Ca2+ will flow out of the SR, down its concentration and into the cytoplasm
2+
ii. Ca then binds to troponin, inducing a conformational change
iii. This allows myosin to now bind to actin, inducing another conformational change
iv. Leads to contraction
d. Seen almost immediately, Ca2+ ATPases start pumping Ca2= back into the SR
i. Allows muscle cell to relax
e. Cytosolic Ca2+ stimulated the contracted state
f. Low cytosolic Ca2+ stimulated the relaxed state
Action Potential During Contraction (slide 46) 04:53
a. Propagation and generation of action potential
b. As soon as Ca2+ is pumped out of the SR, it starts pumping back in
c. Need to go to relaxed state before contracting again
Sensory Organs in Skeletal Muscle (slide 49) 05:54
a. Two structures that help control muscle
i. Muscle Spindles
1. Responds to movement of the muscle
2. Contain intrafusal fibers
a. Move relative to the movement occurring around them
3. Afferent fibers that sense what is occurring and relays information to the brain
4. Example – your arms swing when you walk without you thinking about moving your arms
ii. Golgi Tendon Organs
1. Nerve fibers in tendons that detect stress and tension on tendon
iii. Proprioception
1. Senses pressure and movement for orientation in space
2. Also involved in reflexes
iv. Picture of Muscle Spindle (slide 50,51)
1. Encapsulated structure surrounded by muscle
2. Have nerve fibers and blood vessels
3. Embedded in perimysium
MS-1 FUND 1: 11:00-12:00
Thursday, September 11, 2014
Dr. Cotlin
Muscle Tissue
Transcriber: Deepa Etikala
Editor: Naixin Zhang
Page 2 of 5
Abbreviations: SR = Sarcoplasmic Reticulum
VI. System of Energy Production (slide 52) 09:05
a. Striated muscle gives us very forceful contractions
b. Energy can be gained from fatty acids (oxidative phosphorylation) or from glucose (glycolysis)
c. Also have stored ATP
i. Try to concentrate ATP because it is needed in order to relax the muscle between contractions
ii. At the M line, have creatine kinase which phosphorylates ADP
d. Also, energy is stored as phosphocreatine and glycogen granules to cope with bursts of activity
VII. Myoglobin (slide 53) 10:07
a. The cells that rely on oxidative phosphorylation have high concentrations of myoglobin
i. Myoglobin binds oxygen
1. Similar to a hemoglobin subunit
2. Gives muscle dark red color due to presence of iron
ii. Muscle enriched in myoglobin is muscle that needs a lot of sustained energy
1. So use oxidative phosphorylation
2. Only use glucose when needing quick bits of energy
3. Amount of myoglobin present is an indicator of what type of activity is going on
VIII. Classifications of Fibers (slide 54) 11:02
a. Poultry example
i. Red meat has higher myoglobin concentration
1. In chickens, red meat is in the legs and white meat in breast
2. Birds that fly have the opposite distribution
b. Type I – Slow Oxidative Fibers
i. Also called fatigue resistant, slow contraction
ii. Lots of myoglobin (gives muscle a darker color) means lots of sustained energy
iii. Energy is derived from oxidative phosphorylation of fatty acids
iv. Example: back muscles, red meat
c. Type IIa – Fast Oxidative Glycolytic Fibers
i. Intermediate fibers (mix of other two types)
ii. Have some myoglobin and some glycogen
iii. Fatigue-resistant during peak muscle tension
iv. Example – called medium meat since it is a mix of red and white meat
d. Type IIb – Fast Glycolytic Fibers
i. Much less myoglobin (lighter in color). Higher glycogen granules instead
ii. Rapidly metabolize glucose to lactate
iii. Fatigue prone – related to rapid discontinuous contraction
iv. Example: digits, white meat
e. Most muscle tissue is a mix of these three types
f. Oxidative enzymes are enriched in red fibers (slide 55)
IX. Phosphocreatine-Creatine Cycle (slide 56) 13:30
a. Phosphocreatine is a carrier of phosphate to donate it to ADP to form ATP
i. ADP + phosphocreatine  ATP + creatine
b. Have to regenerate ATP by substrate level phosphorylation in glycolysis or send it back to the mitochondria to
be phosphorylated
c. Creatine helps give a boost of a few rounds of contraction very quickly by assisting in the regeneration of ATP
X. Regeneration, Repair and Diseases of Skeletal Muscle (slide 57) 15:06
a. Muscle cells have the capacity for hypertrophy – increase in size of cells
b. But no hyperplasia (increase in cell number)
i. Regeneration is due to the satellite cells
c. Diseases of skeletal muscle
i. Muscular Dystrophy – mutations in structural proteins
ii. Myasthenia Gravis
1. Autoimmune disease to acetylcholine receptors
2. Antibodies bind to the receptor
a. This prevents acetylcholine from binding, thus inhibiting muscle contraction
iii. Botulism – interferes with acetylcholine release
iv. Neurotoxins
1. Some will bind to acetylcholine receptors and cause contraction in sustained state
XI. Cardiac Muscle (slide 58) 15:57
a. Similar to skeletal muscle in organization of myofibrils
MS-1 FUND 1: 11:00-12:00
Thursday, September 11, 2014
Dr. Cotlin
Muscle Tissue
Transcriber: Deepa Etikala
Editor: Naixin Zhang
Page 3 of 5
Abbreviations: SR = Sarcoplasmic Reticulum
b. Involuntary, unlike voluntary skeletal muscle
i. Propagation from cell to cell
c. Intercalated Disks
i. The point at which two cells are binding and interacting
ii. The branches between cardiac cells that form complex junctions
d. Tend to have multiple nuclei (2-3)
i. Nuclei are centrally located
e. Cross-striated, branching pattern seen
f. Each cell has endomysium, but no organized perimysium or epimysium
XII. Structure of Intercalated Disks (slide 60,61) 17:28
a. Points at which cells meet
b. Junctions may appear as straight lines of step-like pattern forming a transverse and lateral portion
i. Desmosomes and adherens junctions
1. In transverse portion of muscle – runs across fibers at right angles
2. Physically binds the cells together
a. Desmosomes are attachment sites for intermediate filaments. Prevent cells from pulling apart
during constant contraction.
b. Adherens junctions are attachment sites for actin (not pictured). Provides stability.
ii. Gap junctions
1. In lateral portion of muscle – runs parallel to myofilaments
2. Allow for communication between cells through the formation of pores
a. When looking at gap junctions, seems as though the two membranes are fused
b. But they are not! Just in very close contact
3. Used for signal propagation
a. Ions can flow through gap junctions and induce depolarization
b. Gives wave of contraction
c. Also seen in smooth muscle
XIII.
Contractile Features of Cardiac Muscle (slide 65) 19:52
a. Very similar to this feature in skeletal muscle
b. There is organized SR
i. Instead of a triad, the SR and the transverse tubules (T-tubules) form a diad (one to one arrangement)
c. In skeletal muscle, want to flood it with Ca2+ for quick movement
d. Cardiac muscle has more of a graded response
e. Still same series of events
i. Depolarization of T-tubule will trigger depolarization of the SR and allow Ca2+ to rush out to bind to troponin
(different isoform of troponin in cardiac muscle than in skeletal)
1. When diagnosing cardiac episode, look for the presence of this troponin form because when the cell
dies, some will leak out
XIV.
Energy Production in Cardiac Tissue (slide 67) 21:17
a. Rely on fatty acids as major energy source
i. Provides strong reaction and sustained activity
ii. So don’t want to rely heavily on glucose
b. Some regions will have glycogen buildup
i. Used in times of ‘fight or flight’
XV.
Atrial and Ventricular Tissue (slide 69) 22:29
a. Similar to each other, except atrial muscle cells are generally smaller
b. Atrial cells have abundant secretory granules that contain atrial natriuretic factor (ANF)
i. When blood pressure is really high, ANF is released that will act on the kidney to increase Na = and water
loss
ii. Lowers blood pressure
1. Heart is an endocrine organ
a. Endocrine hormone – released in systemic circulation that has a target elsewhere
b. ANF is the hormone of the heart
XVI.
Purkinje Fibers (slide 70) 23:59
a. Specialized cardiac conducting cells that generate and transmit the contractile impulse
i. Have a loose arrangement
ii. Concentrated into nodes that are innervated by both the parasympathetic and sympathetic fibers
XVII. Smooth Muscle Tissue (slide 71) 24:50
a. No striations
MS-1 FUND 1: 11:00-12:00
Thursday, September 11, 2014
Dr. Cotlin
Muscle Tissue
Transcriber: Deepa Etikala
Editor: Naixin Zhang
Page 4 of 5
Abbreviations: SR = Sarcoplasmic Reticulum
b. Still depend on actin and myosin
c. Can be indistinct because they pack tightly
d. Fusiform cells
i. Wide at the center and then taper at the ends
ii. Allows for packing
e. Cells are enclosed by basal lamina
f. Cells are attached by gap junctions for propagation
i. But between all the cells are reticular fibers
1. Reticular fibers are made of collagen III
a. Help keep muscle mass together because smooth muscle is not bound by perimysium or
epimysium (it does have endomysium)
g. Smooth muscle locations:
i. Lining the GI tract from the esophagus to the distal region of the large intestine
ii. Pulmonary tract
iii. Uterus
iv. Bladder and urethra
1. At the tips of urethra, will find skeletal muscle
v. Blood vessels
vi. Dermis of skin (arrector pili in hair follicles)
h. Smooth muscle is controlled by the autonomic nervous system
i. Most smooth muscle will be innervated by parasympathetic and sympathetic
XVIII. Smooth Muscle Cells (slide 73) 29:32
a. Can undergo hyperplasia and hypertrophy (SN: Cardiac muscle cells, like skeletal muscle cells have no regeneration
property – only smooth muscle can undergo proliferation)
XIX.
XX.
XXI.
b. 3-8 um in diameter
c. ~15-500 um in length
i. 20 um in small blood vessels
ii. 500 um in pregnant uterus
d. Cross section stained for reticular fibers (slide 74-76)
i. some cells cross at a very wide point, others at a smaller point (cobblestone appearance)
ii. reticular fibers surround smooth muscle cells so that they don’t rip apart
iii. no desmosomes or adherens, only gap junctions
Contractile Features of Smooth Muscle Cells (slide 77) 31:26
a. Contain rudimentary SR
i. no T tubules
ii. no association between SR and plasma membrane
b. Cardiac needs to be forced contraction
i. smooth muscle acts slower
1. most of the time, there is no urgent need to contract
c. Contain caveolae that act as primitive T tubules
i. Little indentions
ii. But not organized like with triads in skeletal muscle
d. Do have gap junctions for communication
e. Myofilaments crisscross forming a lattice network
i. Thin filaments – actin and tropomyosin (no troponin, instead has calmodulin)
ii. Thick filaments – myosin
Dense Bodies of Smooth Muscle (slide 78) 32:33
a. Crisscrossing of thick and thin fibers
i. In striated muscle, they are all in a row
ii. In smooth muscle, they crisscross
b. Dense bodies can be anchored at the plasma membrane or they can be cytosolic
i. Analogous to the Z lines
1. Actin of the thin filaments is attached at the Z line
c. Contraction causes bunching up and creates a “corkscrew” appearance
d. Thin filaments are closer to the dense bodies and thick filaments are in between the two sides of thin filaments
e. Fundamentals of contraction remain the same – increase in overlap
f. Some are anchored at the plasma membrane and others are internal structures
Smooth Muscle Contraction (slide 81,82) 34:54
a. Requires Ca2+ influx
MS-1 FUND 1: 11:00-12:00
Thursday, September 11, 2014
Dr. Cotlin
Muscle Tissue
Transcriber: Deepa Etikala
Editor: Naixin Zhang
Page 5 of 5
Abbreviations: SR = Sarcoplasmic Reticulum
b. Calmodulin
i. Calcium binding protein in smooth muscle
ii. Myosin Light Chain Kinase (MLCK) enzyme
1. Phosphorylates myosin light chain
c. Ca2+ binds to calmodulin
d. Calmodulin activates MLCKinase
e. Kinase phosphorylates the myosin light chain
i. Causes conformational change which exposes actin binding site and allows contraction to occur
f. When in its unphosphorylated state, myosin cannot bind to actin because its binding site is masked
i. In striated muscle, the binding site on the myosin was being modulated
ii. In smooth muscle, the binding site on the actin head group is being modulated
XXII. Mechanism of Smooth Muscle Contraction (slide 83) 36:48
a. Can induce smooth muscle contraction mechanically, neuronally, hormonally, etc.
b. Hormone example: hormone binds to receptor
i. Most common second messenger pathways in smooth muscle are IP3, G-protein coupled, and Nitric Oxide
pathways
ii. G-protein coupled receptors allow for increase in IP3
iii. Nitric Oxide seen in blood vessels
iv. Schematic:
1. Open Ca2+ channels and Ca2+ rushes in
2. Generation of second messenger that allow for the release of more Ca2+
3. Ca2+ binds to calmodulin
4. Activates MLCK
5. Kinase phosphorylates myosin light chain
6. Trigger contraction
7. Associated phosphatase removes phosphate for relaxation
XXIII. Innervation of Smooth Muscle (slide 84) 38:29
a. Sympathetic and parasympathetic stimulation innervates the tissue
b. Spontaneous activity in the absence of nervous stimuli
c. Stimulate to modulate the contraction
i. Once it is going, doesn’t need constant signal to tell it to go
d. Uses Adrenergic and cholinergic neurotransmitters
XXIV. Regeneration of Muscle Tissue (slide 85) 39:16
a. Skeletal muscle – satellite cells are source for limited regeneration
i. Skeletal muscle cells cannot go through mitosis
ii. After injury, satellite cells are activated, proliferate, and fuse with others to form new muscle fibers
b. Cardiac – no regenerative capacity
i. Don’t have a healthy supply of stem cells in cardiac muscle as we age, so damage is replaced by scar
tissue
c. Smooth – capable of active regenerative response
i. After injury, viable cells undergo mitosis to replace damaged tissue
2 ARS Questions - 39:53
Student Question:
Q: Which muscle types have an endomysium?
A: Every muscle cell has an endomysium. Skeletal muscles are the only ones bundled in perimysium and epimysium.
Cardiac will bundle, but in a fashion that corresponds to its location in the atrium or ventricle. Smooth muscle is comprised
of bands that are not bound by connective tissue.
<END OF LECTURE 43:00>