exam 2- A&P Flashcards
what are we going to get for this exam?
AN A!
What endocrine system
-another control system
-slower than the nervous system (but works together with it)
-signals (traveling long distance) —> binds to receptors
(can be seconds or days before response, long response time)
what makes an endocrine signal
in endocrine systems
distance
signals travel long distance
what is a target cell?
a cell that responds to signals because it has a receptor for the signal molecule
endocrine cell or organ secretes signals into the
interstitial fluid (ISF) which surrounds every cell of the body and signals go to the bloodstream
The expression of specific receptor proteins is crucial to
whether or not cells respond to a particular signal.
not a target cell
has no receptors for the molecules that the secreting cell is releasing
hormones you are familiar
parathyroid hormone- from the thyroid
progesterone- steroid
testosterone- from the testes, a steroid
epinephrine
dopamine
norepinephrine
cortisol
-sterone suffix
steroid
what is the molecule of the hormone
what is it made of
where is the receptor
has to do with what the molecule is made of
hydrophobic molecules (like steroids) have receptors in the cell by hydrophilic molecules (like amino acids and proteins) have receptors at the surface of the cell
class of molecules of hormones
hydrophilic:
proteins
peptides
amino acid derivatives (take 1 amino acid and chemically change it)
hydrophobic:
steroids
lipids
Hydrophilic signal molecules
receptor at plasma membrane
Extracellular signaling molecules (ligands) that can’t cross the membrane and bind to the external portion of transmembrane receptor proteins.
This binding triggers a cascade of events that changes cell activity. (A few examples are altered metabolism, altered gene expression, and altered cell shape of movement).
Fig 16.4 in your book gives an example of a G-protein coupled receptor (GPCR), but not all receptors and signaling cascades work this way.
Hydrophobic
signal molecules
steroids and other lipids
receptor in cytosol or nucleus
1- hydrophobic hormone diffuses into the target cell
2- hormone binds to an intracellular receptor and enters the nucleus of the cell
3- hormone-receptor complex interacts with the DNA to initiate a cellular change
4-
what affects a cell’s response to a hormone (part 1)
blood plasma concentration for the hormone (ie how much hormones are in the blood, and how does this change over time?)
depends on:
1- amount made by the cell
2- amount released to the blood
3- half life- how long before the hormone breaks down
what affects a cell’s response to a hormone (part 2)
receptor population (on the target cell)
1- number of receptors for a given hormone
2- receptors signal affinity (tightness of binding– if bound loosely then there will be less of an effect)
3- other receptors for other hormones
Interactions of Hormones at Target Cells
(Multiple hormones may (and do!) act on the same target at the same time)
1- Permissiveness
2- Synergism
3- Antagonism
Permissiveness
one hormone can’t exert its effect unless another particular hormone is present. M molecule will not work without the P molecule. P gives “permission” to M
Synergism
more than one hormone produces the same effect on the target cell
results in amplification
Antagonism
one or more hormones oppose the “action” of another hormone
ex:
insulin acts when blood glucose levels go down
glucagon acts when blood glucose goes up
Endocrine Organs
hypothalamus
pineal gland
pituitary gland (has an anterior and posterior side)
thyroid gland
parathyroid gland
thymus gland
adrenal (has cortex and medulla)
pancreas
ovaries (for females)
testes (for males)
humeral stimuli for hormone secretion
changes in [ ] in the blood of ions nutrients and H20
Glucose (in the blood) uptake by the pancreatic cell triggers insulin secretion into the bloodstream
neuronal stimuli for hormone secretion
neurotransmitter stimuli secretion
sympathetic neurons stimulate the secretion of epinephrine and norepinephrine out from the adrenal medulla cell
from picture: the axon terminal of the sympathetic neuron releases a neurotransmitter that binds to the receptors of the adrenal medulla cell. The adrenal medulla cell now releases epinephrine and norepinephrine
hormonal stimuli for hormone secretion
hormonal stimulation: growth hormone-releasing hormone (GHRH) stimulates the secretion of growth hormone (GH) out from an anterior pituitary cell
hormonal inhibition: somatostatin inhibits the secretion of growth hormone from an anterior pituitary cell
Maintaining homeostasis: regulation of hormone secretion by negative feedback loops.
stimulus: a regulated physiological variable deviated from its normal range- goes below
receptor: receptors on endocrine cells detect the deviation of the variable
control center: the stimulated control center (often the endocrine cell) increases or decreases its secretion of a particular hormone
effector/response: the hormone triggers a response in its target cells that moves conditions toward the normal range
hypothalamus and pituitary
then pituitary (pituitary = adenohypophysis + neurohypophysis)
structures of the diencephalon
thalamus
epithalamus
pineal gland
brainstem
subthalamus
mamillary body
pituitary gland
infundibulum
hypothalamus
locations of the hypothalamus and pituitary gland in the brain
sella turcica of sphenoid bone
structure of hypothalamus
optic chiasma
anterior pituitary = adenohypophysis – front of face
posterior pituitary = neurohypophysis —back of face
infundibulum
hypothalamus
another name for the pituitary (which sits in sella turcica)
hypophysis
pea on a stalk
stalk = infundibulum
some processes integrated by the endocrine system
-growth and development
-cellular metabolism/energy balance
-mobilization of body defenses
-maintenance of electrolyte, H2O, and nutrient contentl of blood
-reproduction
ADH
What does it stand for
what are its source, target, and effect
Anti-Diuretic hormone
source- hypothalamus, released at posterior pituitary (neurohypophysis)
target- kidneys
effect- lessens urine production
also known as vasopressin- to tighten blood vessels
Oxytocin
what are its source, target, and effect
source- hypothalamus, posterior pituitary gland (neurohypophysis)
target: breasts and uterus (also acts as neurotransmitter for the brain)
effects: milk released from breasts, uterine contractions (positive feedback mechanism- during labor, baby’s head pushes against the birth canal, causes the uterus to contract, causes more stretching, causes more contractions, causes more contractions until the baby’s is born!)
to induce labor, synthetic oxytocin is administered
ADH and Oxytocin similarity
They are both 9 amino acids long, differ by 2 amino acids—have very different effects (one is milk and contractions, one is urine lessener)
circulatory system flow
heart
to
blood aorta
to
arteries
to
arterioles
to
capillaries (tiny vessels)
to
venules
to
veins
to
heart
portal system flow
capillaries (tiny vessels)
to
venules
to
veins
happens in the brain?
examples of the portal system
hypothalamic-hypophyseal system
liver hepaticportal system
RHs and IHs
releasing hormones (RHs) and Inhibiting hormones (IHs)
RHs and IHs
source
target
effect
source: hypothalamus
target: anterior pituitary gland
effect: stimulator inhibit the release of anterior pituitary hormones
types of hormones
tropic and trophic
tropic
affects the release of hormones from another endocrine gland
trophic
affects the growth of another gland
Trophic
Affects the growth of another Gland
Hormone
Substances that travel long distances
Cells of the brain that secret signals
Neurons and neurosecretory cells
Neurohormones are secreted by
Neurosecretory cells and travel through the bloodstream
Signals are released after an action potential and picked up by the blood stream
Some hypothalamic neurons are
Neurosecretory cells that release hormones
How many hormone are released at the posterior pituitary gland (AKA neurohypophysis)
2 hormones released into the bloodstream from posterior pituitary gland
How many hormones are released to the hypophyseal portal system
Several hormones (releasing and inhibiting hormones) are released to hypophyseal portal system
Release of hypothalamic hormones at the posterior pituitary
1- hypothalamic neurons make either ADH or oxytocin
2- the hormones travel through the hypothalamic axons in the infundibulum
3- ADH and oxytocin are stored in the axon terminals in the posterior pituitary
4- the hormones are secreted into the blood when the hypothalamic neurons fire action potentials and are picked up in the bloodstream
Hypothalamic-hypophyseal portal system
Hypothalamic capillary bed
Portal veins
Anterior pituitary capillary bed
Hypothalamic hormones released to the hypothalamic-hypophyseal portal system
1- hypothalamic neurons secrete releasing and inhibiting hormones into the hypothalamic capillary bed
2- hormones travel through portal veins in the infundibulum
3- hypothalamic hormones exit the anterior pituitary capillary bed to bind to receptors on anterior pituitary cells
4- hypothalamic hormones stimulate or inhibit secretion of hormones from the anterior pituitary cells to systemic circulation
Hormones that are made and released by the anterior pituitary
TSH
ACTH
Gonadotropins (FSH & LH)
Growth hormone (GH)
Prolactin
TSH
Name & target
thyroid stimulating hormone (AKA thryotropin)
Target: thyroid
ACTH
Name & target
Adrenal corticotropic hormone
Adrenal glands
Gonadotropins
Target
FSH & LH
effects ovaries and testes
Source of TSH, ACTH and gonadotropins
Anterior pituitary gland
3 tiers of feedback
On cheat sheet
Prolactin
Source
Target
Effect
PRL
Source- anterior pituitary gland
Target- mammary gland/breast
Effect- produce milk.
Growth hormone
Source
Target
Effect
Source- anterior pituitary gland
Target- bones, muscles, liver, adipose tissue
Effect- energy usage, stimulates bone and muscle growth
Effects of growth hormone
Metabolic effects (opposite of insulin)
Elevate nutrient levels in blood
Changes how muscle, liver and fat changes how they deal with nutrients
Short term effects of GH
- GH released from anterior pituitary
- goes to the blood stream
- inhibits glucose uptake by skeletal muscle
- stimulates gluconeogenesis in the liver
Both cause increased blood glucose concentration - stimulates lipolysis in the fat
Increased blood fatty acid concentration
Indirect and long term effects of GH
target- bones, muscles, adipose tissue released IGF (insulin-like growth factor)
Bone- cause collagen formation (bony matrix deposition; bone growth)
SKM- stimulates mass increase
Body cells- nutrient uptake and use-> protein production and cell division, DNA synthesis
GH released from anterior pituitary gland
Goes into blood stream
Causes IGF Release by the liver, muscle, bone, and other tissues which:
Stimulates glucose uptake by body cells causes deceased blood glucose concentration
Stimulates cell division, increased growth of bone and other tissues
Stimulates protein synthesis, increased mass of muscle and other tissues
What does TSH cause thyroid to do
Binds receptors on follicle cells of the thyroid
TSH target: thyroid
1.) cells respond by scenting stored T3 and T4
2.) cells respond by synthesizing more colloid
How is T3 and T4 made
1.) iodide (I-) actively transported into follicle cells through the follicle cells into the colloid
2) in the colloid, iodide is deionized (so it goes from I minus to just I) and attaches to the thyroglobulin
3) thyroglobulin + iodine (3 or 4) in endocytosed
4) lysosome make thyroglobulin + iodine substance into T3 and T4. T3 and T4 can leave lysosome and can be secreted/released.
By having so many steps, this process is regulated
What is mostly made, T3 or T4
And what is T3 and T4
What is the nature of T3 and T4
T3 is thyroglobulin with 3 iodines
T4 is thyroglobulin with 4 iodines
Most of what comes out is T4 but is easily converted to T3 in the tissues (T3 is active form and bind tighter)
T3 and T4 are hydrophobic so their receptors are in the cell but they need protein carriers in the blood stream
the thyroid gland
up in the neck
largest endocrine gland
no exocrine function
only secretes hormones to to blood stream
gross structure of the thyroid
butterfly shape
larynx
superior thyroid artery
thyroid gland (right lobe)
isthmus
trachea
adrenal glands
small, triangular-shaped glands located on top of both kidneys. Adrenal glands produce hormones that help regulate your metabolism, immune system, blood pressure, response to stress, and other essential functions.
-ren = kidney
two parts of the adrenal gland
medulla and cortex
hormones made in the cortex (outer layer) of the adrenal gland
corticosteroids
mineral corticoids
glucocorticoids
sex hormones (like estrogen)
-corticoid = cortex
hormones made in the medulla (inner layer) of the adrenal gland
epinephrine
norepinephrine
these are catecholamines
both bind to the same receptors just at different affinities
receptors in the plasma membrane
mineral corticoids & an example of one
a hormone made at the cortex of the adrenal gland
ex: aldosterone
what does aldosterone do
control ion/mineral levels in the blood (Na+ and K+)
control blood volume and blood pressure (as BV goes up, so does BP)
Target of aldosterone
kidney
what does aldosterone do
keep Na+ and H2O in the blood instead of allowing them to go through the urine at the same time, K+ is going through the urine
result: blood volume and blood pressure increase but urine decreases, helps to maintain blood pressure
increase blood pressure
stimulus of aldosterone
decrease in blood pressure
glucocorticoids
example of it: cortisol
gluco = sugar
corticoids = cortex of adrenal gland
maintains blood nutrient (sugar) levels, needed for prolonged stress and uses energy resources
tow types of stress
acute - reaction is to respond, increased heart rate, breathing Is higher, blood pressure is increased
prolonged (chronic) - reaction is to resist, increase nutrient availability in the blood
stimuli for cortisol release
day/night cycle
stress
corticosteroid release control
CRH (cortisol-releasing hormone) from the hypothalamus
CRH causes ACTH release from neurohypophysis which causes adrenal glands to secrete corticosteroids
sarcoma
Sarcoma is an uncommon group of cancers which arise in the bones, and connective tissue such as fat and muscle.
sarcopenia
loss of muscle tissue as a natural part of the aging process.
rhabdomyolysis
A breakdown of muscle tissue that releases a damaging protein (myoglobin) into the blood.
myoglobin is toxic to kidney
paralysis
the loss of the ability to move some or all of your body
rhabdomyolysis
A breakdown of muscle tissue that releases a damaging protein (myoglobin) into the blood.
myoglobin is toxic to the kidney
hematuria
blood in urine
glycosuria
a condition characterized by an excess of sugar in the urine, typically associated with diabetes or kidney disease.
control of thyroid hormone release
stimulus: decreased levels of free T3 and T4 in the blood and exposure to cold
receptor: receptors in the hypothalamus detect a change
first-tier control: hypothalamus secretes TRH
Second-tier control: anterior pituitary secretes TSH
third-tier control: thyroid gland is stimulated to–produce T3 and T4, secrete T3 and T4 into the blood, grow and develop
effects: increased levels of T3 and T4 in the blood which causes increase in metabolic rate
negative feedback of thyroid gland
as T3 and T4 LEVELS RISE, THE HYPOTHALAMUS DECREASES try SECRETION AND THE ANTERIOR PITUITARY DECREASES TSH SECRETION
TSH
thyroid stimulating hormone
TRH
Thyrotropin releasing hormone
thyroid hormones
T3 & T4
what does T4 stand for
thyroxine
what does T3 stand for
triiodothyronine
what do thyroid hormones (T3 & T4) do
made in the follicle cells of the thyroid gland
affect almost every cell in the body
increase basal metabolic rate (BMR) (which counts as ATP) and heat production
regulate tissue growth and development
need for normal skeleton and reproduction
maintain blood pressure– indirect effect by decreasing # of receptors on vessels (receptor for norepinephrine and epinephrine)
info on follicle cells of the thyroid gland
hormones made: triiodothyronine (T3) and thyroxine (T4)
stimulus for secretion:
TSH from the anterior pituitary
inhibitors of secretion:
increases levels of T3 and T4 inhibit TRH and TSH
Target tissue: nearly every cell in the body
effects:
-set the basal metabolic rate
-thermoregulation
-growth and development
-synergism with Sympathetic nervous system
follicle cells, colloid and parafollicular cells
follicle is the balloon, colloid fill the balloon
cell around the follicle are follicle cells
parafollicular cells are btwn the follicle cells
blood vessels and the thyroid
there are blood vessels between every thyroid follicle containing a colloid
the hormones made by the thyroid (triiodothyronine and thyroxine) are transported by the blood vessels
thyroid cancer
easily treated
Surgical removal followed by another therapy
surgical removal of thyroid is followed by another therapy
Can you think of a way to specifically target any leftover thyroid cells for destruction?
give them radioactive iodine, will only be taken by thyroid cells
The Parathyroid Glands
circles On top of the thyroid
PTH is the most important [calcium] in the blood
Regulation of blood calcium ion concentration by a negative feedback loop
stimulus: blood Ca2+ level decreases below the normal range
receptor: chief cells in the parathyroid gland detect a low blood Ca2+ level
control center: chief cells increase parathyroid hormone secretion
effector/response: osteoclasts are stimulated to degrade bone, increasing Ca2+ resorption, more Ca2+ are reabsorbed from the fluid in the kidneys, kidneys activate calcitriol, increasing Ca2+ absorption in the small intestine
in homeostatic range: as the blood Ca2+ level returns to normal, feedback to chief cells decreases PTH secretion
effects of aldosterone
aldosterone release from adrenal cortex
Na+ and Cl- move from fluid in the kidney tubules to the blood to maintain electrolyte balance, H2O follows, helping to maintain blood pressure
K+ is transported from the blood into the fluid in the kidney tubules
H+ is transported from the blood into the fluid in the kidney tubules
K+ & H+ are excreted in urine to help maintain electrolyte and acid-base balance
short-term stress
stress triggers nerve impulses in the hypothalamus
the nerve impulses are connected to the spinal cord
the spinal cord connected to the preganglionic sympathetic fibers
adrenal medulla (secretes amino acid based hormones)
catecholamines (EP & NE)
short-term responses:
-heart rate & blood pressure increase
-bronchioles dilate
-liver converts glycogen to glucose and releases glucose to blood
-blood flow changes, reducing digestive system activity and urine output
-metabolic rate increases
prolonged stress
stress triggers hypothalamus
CRH (corticotropin-releasing hormone)
corticotropic cells of the anterior pituitary release ACTH to target the blood
andrenal cortex (sceretes steroid hromones) release mineralcorticoids and glucocorticoids
long-term stress:
-kidneys retain sodium and water
-blood volume and blood pressure rise
-proteins and fats converted to glucose or broken down for energy
-blood glucose increases
-immune system suppressed
the big picture of the hormonal response to stress
epinephrine and glucagon are synergistic
both cause to be released into the blood, but when they act together the glucose released is about 150% of that when each acts alone
the pineal gland
daily rhythms (entrained/ set light/dark)
diurnal
circadian
the main hypothalamic nuclei
-supraoptic nucleus
-suprachiasmatic nucleus
-paraventricular nucleus
paraventricular nucleus
oxytocin comes from neuroendocrine cells here
supraoptic nucleus
ADH comes from neuroendocrine cells here
suprachiasmatic nucleus
the master circadian regulator, found in the hypothalamus
melatonin release
retina - intrinsically photosensitive retinal ganglion cell -ipRGCs (not the same as the rods and cones these are other cells)
the suprachiasmatic nucleus (SCN)
neurons here show spontaneous circadian rhythms and electrical activity. they are with each other via input from ipRGCs.
Cells have melatonin receptors.
neuronal input into the pineal gland
Makes and releases melatonin
endocrine signal- Melatonin is sent to many target cells.
Can help to “set their clocks” to daylight time.
(Note that melatonin can also come from other cells than those in the pineal gland, this is also true for many other hormones – they may be made and released from various body tissues).
are skeletal muscles multinucleate
yes!
structure of a skeletal muscle
bone
muscle fascia
fascicle
muscle cell fiber
epimysium
perimysium
endomysium
muscle vocab.
myo
mys
sarco
fascile: bundle
mus
musculous
muscle fascia
fascicle
muscle cell fiber
fascia
mysium
muscle fiber- connective tissue
fascicle - bundles
muscle cell fiber - individual muscle cell aka myofiber & myocyte
muscle cells are long and rope-like
fascia - sheet of connective tissue
mysium - a layer of dense fibrous connective tissue that surrounds the entire muscle
Remember prefixes you have seen before:
epi-, peri-, endo-
epi- upon
peri- between
endo- inside
endomysium, perimysium & endomysium info.
Endomysium is extracellular matrix (proteins) of myofibers/myocytes.
The perimysium surrounds fascicles – bundles of 10 to 100 myofibers.
The epimysium is continuous with the fascia (not shown) – fascia is the most superfinical connective tissue sheath, fascia separates individual muscles. You saw this in lab
Peri- and epimysium along with fascia merge together to form the tendons that attach muscle to bones.
The epi- and perimysium merge together to form
Microscopic anatomy of a skeletal myofiber: overview
muscle fiber -
1 muscle cell
complex and highly structured
myofibers
sarcolema
sarcoplasmic reticulum
mitochondria
myofibrils
what are thick and thin filaments made of
sarcolema: muscle membrane ; plasma membrane
sarcoplasmic reticulum stores Ca2+
many nuclei
mitochondria (# depends on how it gets ATP)
myofibrils - thin filaments and thin filaments
thick filaments are made of myosin
thin filaments
what are thin filaments made of
F-actin = filamentous actin
troponin
tropomyosin
break down of muscle
muscle
fascile
muscle fiber
myofibril
myofilaments
what are myofilaments made of
thick filament
thin filament
elastic filament
Z-disk
M-line
Sarcomere
Z-disk: boundary of a sarcomere
M-line: a thin dark line across the center of the H zone of a striated muscle fiber.
Sarcomere: a structural unit of a myofibril in striated muscle, consisting of a dark band and the nearer half of each adjacent pale band.
The myofiber (AKA myocyte) components
sarcolemma
sarcoplasm
myofibril
sarcoplasmic reticulum
mitochondrion
nucleus
sarcolemma: muscle cell membrane
sarcoplasm: the cytoplasm of striated muscle cells.
myofibril: a basic rod-like organelle of a muscle cell.
sarcoplasmic reticulum: a specialized form of the endoplasmic reticulum of muscle cells, dedicated to calcium ion (Ca2+) handling, necessary for muscle contraction and relaxation.
mitochondrion: an organelle found in large numbers in most cells, in which the biochemical processes of respiration and energy production occur. It has a double membrane, the inner layer being folded inward to form layers
nucleus: the central and most important part of an object, movement, or group, forming the basis for its activity and growth.
the triad of muscle consists of
T-Tubule
Terminal cisterns of Sarcoplasmic reticulum
T-tubule
stands for transverse tubule
deep invagination (folding) of the sarcolemma
terminal cisterns of SR
SR = sarcoplasmic reticulum
on either side of the T-Tubule
Cistern
means “tank” or “reservoir”.
”. Here the terminal cisternae are the areas of the sarcoplasmic reticulum next to the T-tubule.
sarcomere
contractile unit of a muscle fiber goes from Z-line to Z-line
light/dark of the sarcomere is dependent on fiber protein overlap
what are muscle fibers made of
what are myofibrils made of
what are thin filaments made of
what are thick filaments made of
what are elastic filaments made of
muscle fibers are made of myofibrils
myofibrils are made of thin, thick filaments and elastic filaments
thick filaments made of myosin tails and myosin heads
thin filaments made of troponin, tropomyosin (needed for skeletal muscle tension) & actin (has actin subunit and actin active site)
elastic filaments are made of titin
myosin heads and tails is a what
it is a molecular motor protein that changes shape (ATP to ADP) – this drives shape change which is used to move things
Simple cartoon of the sliding-filament mechanism:
the thin and thick filaments slide past one another to shorten the sarcomere, Z-line to Z-line
defines the boundary of the sarcomere in striated muscle and bisects the I-band of neighboring sarcomeres, when a muscle contract, the distance between the Z discs is reduced
Key things needed for filaments to “slide” past each other (.e. for the myosin heads to “walk” along the actin):
Ca2+ & ATP
What is Ca2+ important for?
What is the “store” of Ca2+ in the myofiber?
Ca2+ is important for actin (of the thin filament) and myosin interaction (of thick filaments– when the thick and thin filaments slide closer to each other then the muscle contracts but when they get further then the muscle relaxes)
Ca2+ is stored in the sarcoplasmic reticulum
why is ATP needed for filaments to “slide” past each other
needed to change the shape of myosin; allowing for the myosin of the thick filament to attach and detach from the actin of the thin filament
proteins of thick filaments
myosin (for myosin heads and myosin tails)
proteins for thin filaments
troponin, tropomyosin, actin
The cross-bridge cycle
1- Ca2+ floods into the sarcomere
2 - troponin binds to Ca2+ and changes shape to interact with tropomyosin
(troponin interacts with tropomyosin)
3 - actin active sites are exposed and ready for myosin binding and the myosin heads bind to actin!!!!!!!
4 - the myosin head raises as it attaches to the actin
the ATP-driven shape change in myosin heads allows myosin heads to “walk” along actin filaments.
1 - ATP hydrolysis (ATP can be hydrolyzed to ADP and Pi by the addition of water, releasing energy.) “cocks” the myosin head- so the myosin head is in a straight position
2 - the myosin head binds to actin and is attached to ADP & P
3 - The power stroke (when the myosin moves forward abruptly) occurs when the ADP and phosphate detach from the myosin head; myosin pulls actin toward the center of the sarcomere; both the actin and myosin head move forward
4 - ATP goes onto the myosin head and breaks the attachment of the myosin head to actin
Remember the key things necessary for filaments to “slide” past each other (i.e. for the myosin heads to “walk” along the actin filaments):
ATP
Ca2+
How does Ca2+ get into the sarcoplasm of the myofiber in order for a muscle to contract? In other words, how does it get out of the sarcoplasmic reticulum store?
by the excitation-contraction coupling
The neuromuscular junction
a synaptic connection between the terminal end of a motor nerve and a muscle
What will happen at the neuromuscular junction
A motor neuron will cause an action potential to happen @ skeletal muscle
The cells that can have action potentials are: neurons, cardiac muscle & skeletal muscle
What is at the neuromuscular junction/what does it look like
A motor neuron is connected to skeletal muscle
What it looks like: the axon terminal of the motor muscle forms a synapse (space where neurotransmitter can pass through) to the muscle fiber of the skeletal muscle
At the motor neuron
-axon terminal
-synaptic vesicles
-acetylcholine (ACh) molecules
-ECF (extra cellular fluid)
At the muscle fiber (motor end plate of muscle fiber)
-sarcolemma
-ACh receptor
-cytosol
-synaptic cleft
Excitation phase: events at the neuromuscular junction
ACh is exocytosed from the axon terminal out of the vesicle
ACh binds to the binding site on receptor (ligand gated ion channel) which is at the motor end plate
For muscular system
Neurotransmitter = acetylcholine (ACh)
AChR = acetylcholine receptor, it is a Ligand gated ion channel so when it binds the ACh it will open
It is considered to be ionotropic
Ionotropic AChR
Ionotropic receptors
Ligand-gated ion channels, also commonly referred to as ionotropic receptors
3 things to decrease [ACh]
Taken back up by the motor neuron
Broken down by acetylcholinesterase (AChE)
Diffuse away
Action potentials at the neuromuscular junction
Goes in all directions
1- The end plate potential stimulates an action potential to open Na+ Channels for Na+ to open
2- the action potential is propagated down T-tubules of the triad (which has sarcoplasmic reticulum both sides of the T-tubules)
3- T-tubule depolarization leads to the opening of Ca+ channels in the SR, and Ca+ enter the cytosol of the T-tubule; voltage sensitive protein changes shape in response to action potential, this opens calcium channels on SR membrane for Ca+ to move into the cytoplasmic reticulum
Stages of an action potential
Resting stage: before a stimulus arrives, the membrane is at the resting membrane potential (RMP) and voltage gated Na+ and K+ channels are closed
Depolarization stage: in response to a stimulus voltage gated Na+ enter the cell making the membrane potent Ian less negative
Repolarization stage Na+ channels close while voltage gated K+ channels open the K+ leave the cell, making the membrane potential more negative again
Preparation for contraction: regulatory events of the myofibril
A- the Ca2+ channels Is closed so Ca2+ cannot flow into the SR. The T-tubule is negative inside and At this points, the muscle is at rest and the tropomyosin blocks actin’s sites because the troponin is not bound by the Ca2+
B- the Ca2+ channels are open and it flows into the space between the SR and the T-tubule. This space then becomes positive and the T-tubule becomes negative which depolarizes the T-tubule. after stimulation, Ca2+ releases from the troponin and causes the active sites to be exposed; Ca2+ bind to troponin and the tropomyosin moves and the active sites of actin are exposed
Summary of neuromuscular junction
1- excitation: ACh from axon terminal triggers an end plate action potential in the motor end plate
2- excitation contraction coupling: the resulting action potential in the sarcolemma travels down the T-tubules and triggers Ca2+ relaxes from the SR into the cytosol
3- preparation for contraction: Ca2+ binds to troponin which moves tropomyosin away from the active sites of actin
4- contraction: actin and myosin head bind and myosin head undergoes a power stroke, ATP detaches actin and myosin head and the cycle repeats leading to contraction of the muscle
5- relaxation- the neuron stops releasing ACh and the AChE degrades the ACh in the synaptic cleft. The cytosolic concentration of Ca2+ returns to the resting level and the active sites of actin are blocked and the muscle fiber relaxes
The aftermath:
What happens when muscle AP stops
When the muscle AP ceases:
-voltage sensitive T-tubule proteins returns to original shape
-Ca2+ channels on SR close
-Ca2+ levels in the sarcoplasm fall as Ca2+ is continually pumped into SR
-with low Ca2+ in the cytosol (sarcoplasm) then troponin is unbound to Ca2+ and tropomyosin blocks active site on actin
Each time when an AP arrives at the neuromuscular junction the sequence of EC coupling is repeated
A little more information on motor units
A motor unit consists of one motor neuron and all the muscle fibers it innervates (talks to)
Spinal cord has a couple axons of motor neurons
The motor neurons are attached to muscle fibers forming neuromuscular junctions
The muscle fibers are in the fascicle
One axon could be attached to 3 even 5 muscle fibers
A motor unit in real life
Axon terminals at neuromuscular junction
Muscle fibers
Branching axon to motor unit
Branching axon terminals form neuromuscular junctions with muscle fibers
muscles shorten (sliding filament model)
pull rather than push – antagonistic muscles moving in one direction or the other
muscles can lengthen when force is put on them and can stretch
the connective tissue around the muscle is epimysium
epimysium
The epimysium is a thick connective tissue layer composed of coarse collagen fibers in a proteoglycan matrix. The epimysium surrounds the entire muscle and defines its volume. The arrangement of collagen fibers in the epimysium varies between forces of different shapes and functions.
Tension
force a muscle is able to develop; force exerted by a contracting muscle
load
the opposing force, exerted on the muscle
How myofilament sliding leads to whole muscle contraction.
the connective tissue help to transmit force
1- sarcomeres contract (Z-lines move together), transmitting tension to the sarcolemma and endomysium
2- the tension of the muscle fibers is transmitted to the fascicle (which the bundle of muscle fibers) and the perimysium
3- the tension in the fascicles is transmitted to the connective tissues of the whole muscle, leading to pulling on the bones and causing movement
anatomy of the muscle
fascicle- the bundle of muscle fibers
muscle fiber- collection of myofibrils
myofibrils- thin (troponin, tropomyosin & actin) and thick (myosin heads and myosin tails) filaments that slide past each other
Motor unit
made up of a motor neuron and all of the skeletal muscle fibers innervated by the neuron’s axon terminals, including the neuromuscular junction
Each muscle (organ) is innervated
by ≥ 1 motor nerve
Number of fibers that a neuron contacts can be from as low as 4 and as many as several hundred.
When a motor neuron fires,
all of the muscle fibers it innervates contract
Myogram (Laboratory record of contractile activity) shows the three phases of an isometric twitch
1- latent period- action potential spreads through the sarcolemma
2- contraction period- tension rapidly increases
3- relaxation period- tension decreases as Ca2+ are pumped back into SR
Comparison of the relative duration of twitch responses of three muscles (the point here is that different muscles can have different responses.)
soleus
gastrocnemius
extraocular muscle
soleus- 200 ms
gastrocnemius- 80 ms
extraocular muscle- 20 ms
cycle of twitch
signal (AP)
Twitch (latent period- contraction - relaxation)
signal (AP)
Twitch (latent period- contraction - relaxation)
Twitch over
Changing the firing rate of motor neuron action potentials
Allows for graded responses –
muscle contractions that are smooth and vary in strength with different demands
how to get muscles to contract- *with different amounts of force?
*for varying periods of time?
Stimulus frequency (how much time between action potentials?)
If AP are in SLOW succession
muscle fibers have time to return to baseline relaxation before they are stimulated to contract again
This is like the circular diagram of a twitch
If AP are in RAPID succession
The relaxation time between twitches becomes shorter and shorter (or muscle may not relax completely)
Muscle is already partially contracted, then more Ca2+ is added to sarcoplasm
second twitch will be stronger than the first
wave summation infuses tetanus
If another stimulus is applied before the muscle relaxes completely, then more tension results.
This is wave (or temporal) summation and results in unfused (or incomplete) tetanus.
the muscle fiber is not allowed to relax completely between stimuli; fiber stimulated about 50 times per second
wave summation: fused tetanus
At higher stimulus frequencies, there is no relaxation between stimuli.
This is fused (complete) tetanus.
muscle fiber is not allowed to relax between stimuli; fiber stimulated 80-100 time per second, which generated sustained contraction and maximal tension
Changing the number of motor units in play
Controls force of contraction more precisely than wave summation
Recruitment (multiple motor unit summation)
Subthreshold stimulus–
No observable contractions produced
Threshold stimulus—
Observable contraction occurs
After this point muscle contracts more vigorously as stimulus strength increases
Maximal stimulus–
Strongest stimulus that increases contractile force
AT THIS POINT – all of the muscle’s motor units are recruited.
The size principle of recruitment.
Motor
unit 1
recruited
(small
fibers)
Motor
unit 2
recruited
(medium
fibers)
Motor
unit 3
recruited
(large
fibers)
The length-tension relationship
The number of cross-bridges that can form in a sarcomere will affect the amount of tension a twitch can produce
Types of muscle contractions
Tension is generated in all situations
1- isotonic concentric contraction- tension force generating- muscle shortens
2- isotonic eccentric contraction- common: generation of force- muscle lengthens
3- isotonic contraction- load force opposing- muscle stays the same length
functions of skeletal muscle
–movement
–maintain posture
–generate heat (if body temp. goes down you shiver 2 generate heat)
–respiration (breathing)- diaphragm is a skeletal muscle
-pumping blood- muscular pump (not the heart)
different types of skeletal muscle fibers (individual cell in muscle as an organ)
type 1- slow-twitch = slow oxidative
type 2- fast-twitch = glycolytic
what is the preferred use of energy for muscles
what are its other fuels
glucose
other fuels: fat and amino acids
type of cellular chemical reactions for generating ATP;
2 ways to make ATP
Oxidative vs glycolytic
oxidative method of making ATP
Type 1 method- slow-twitch = slow oxidative
oxygen use to make ATP
Oxidative phosphorylation
O2 is required
Aerobic respiration
makes much more ATP than glycolysis does
occurs in mitochondria, broken down further and ATP is made
glycolytic method of making ATP
Glycolysis: glucose breakdown will make ATP and some waste product like lactic acid
occurs in cytosol
does not require O2 so it is anaerobic respiration
other way to make ATP besides
oxidative & glycolytic method
creatine phosphate + ADT goes to creatine + ATP
Enzyme that catalyzes this process is creatine kinase
this process occurs in the cytosol and mitochondria
ATP production
in different parts of the skeletal muscle
glucose comes the bloodstream; also stored in muscle as glycogen
O2 comes from bloodstream; also stored in myoglobin (muscle protein) in muscles
in cytosol: glycolysis occurs, glucose is required, anaerobic process, no O2 required
Also: Creatine kinase (catalyzes the formation of ATP from ADP and Pi)
-creatine phosphate is required
-Anaerobic
There are actually creatine kinase isoforms in both cytosol and mitochondria
In mitochondria:
Aerobic cellular respiration.
oxygen is required
Preferred fuel = glucose
* Yields ATP (16X more than glycolysis)
Sources of energy for muscle fibers
immediate energy sources:
from stores ATP, ATP is used in the myofibril cell & from creatine phosphate being added to ADP to make creatine and ATP to be used for myofibril; creatine kinase catalyzes the transfer of a phosphate group from creatine phosphate producing ATP (and creatine)
glycolytic and oxidative energy sources: Glycolytic = glycolysis breaks down each glucose molecule from the blood stream to produce 2 ATP to be used by the myofibril. Oxidative = break down fuel molecules to generate many ATP via oxidative reactions in the mitochondria
What is myoglobin
an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue
can be toxic and a large amount of myoglobin can damage the kidneys and even cause acute renal failure.
Where do fuels for making ATP come from?
Glycogen (storage form of glucose) is found in muscle (in glycosomes) (glycogen also stored in liver)
Glucose comes from blood stream
Other nutrient fuels also come in from bloodstream
Oxygen is from blood stream or from myoglobin
Myoglobin in muscles is an oxygen-binding protein, “sink” for oxygen
(like a store)
energy sources used during short-duration exercise AKA sprint
mostly anaerobic
6 seconds: ATP stored in muscle is used first
10 seconds: ATP is formed from creatine phosphate and ADP (direct phosphorylation)
30-40 seconds to end of exercise: glycogen stored in muscles is broken down to glucose which is oxidized to generate ATP (anaerobic pathway)
energy sources used during prolonged-duration exercise AKA marathon
aerobic - mitochondria
hours: ATP is generated by breakdown of several nutrient energy fuels by aerobic pathway
Delayed onset muscle soreness (DOMS)
workout then next day you’re sore
Definition of muscle fatigue
Physiological inability to contract (even if muscle is still receiving neuronal input)
cannot generate more tension even if neurons are dumping acetylcholine
(muscle don’t run out of ATP not normally)
in muscles, pH is regulated
so we don’t get acidic muscles
Even as lactic acid may be produced in skeletal muscles during anaerobic ATP production, pH is regulated and kept within normal limits in all but extreme exertion cases.
fatigue and DOMS are not the same thing
Speed and duration of contraction depends on
ATP producing pathways
&
ATPase in the myosin head groups
these things vary for different fiber types
Comparison of type I (slow-twitch) and type II (fast-twitch) muscle fibers.
type I fibers need a lot of oxygen to fuel long periods of movement (marathon), they have lots of myoglobin. And myoglobin, it turns out, is richly pigmented, meaning an abundance of this protein gives dark meat its brown shading- aerobic process and oxygen is from the bloodstream or on myoglobin
type II fibers on the other hand, get their fuel from glycogen to make glucose to make their ATP. this is for short exercises which are sprints
metabolic characteristic & structural characteristics of slow oxidative fibers
type I
metabolic characteristic
Speed of contraction: slow
myosin ATPase activity: slow
Structural characteristics
color: red
fiber diameter: small
mitochondria: many
capillaries: many
metabolic characteristic & structural characteristics of fast oxidative & glycolytic fibers
type II
Speed of contraction: fast
myosin ATPase activity: fast
type II fast oxidative
color: red to pink
fiber diameter: intermediate
mitochondria: many
capillaries: many
type II fast oxidative
color: white (pale)
fiber diameter: large
mitochondria: few
capillaries: few
muscle hypertrophy and atrophy (discussion)
muscle hypertrophy - grow bigger; grow in size
atrophy - non-growth, muscle size loss
what does physical activity (endurance & resistance) do to the muscles
endurance training (long journey, use more O2, slow twitch)- end up in increase in mitochondria, blood vessels, mitochondria proteins, enzymes needed for oxidative phosphorylation
resistance training (weights & fast twitch) - some biochem changes, increase size of fibers, satellite cell (muscle stem cells) activation
changes in muscle fibers due to training and disuse.
normal use: blood vessel myofibril and mitochondrion in tact
endurance training: increase oxidative enzymes, increases number of mitochondria and mitochondrial proteins, increased number of blood vessel
resistance training: increased number of myofibrils, increased diameter of muscle fiber and myofibrils
disuse: decreased oxidative enzymes, deceased number of myofibrils and decreased diameter of muscle fiber
Effects of endurance Exercise:
-(aerobic)
-Increase frequency of motor unit activation
-Smaller increase in force production
-End up: increased blood vessels, mitochondria, mitochondrial proteins, oxidative enzymes
-Used to be thought this didn’t cause muscle hypertrophy, however this does not seem to be the case necessarily (in other words, can get some hypertrophy)
Effects of resistance Exercise:
-(anaerobic)
-Increase frequency of motor unit activation (to a small extent)
-Larger increase in force production
-End up: biochemical changes, satellite cell activation, increase in size of myofibers hypertrophy
players in muscle hypertrophy
1- satellite cells
2- protein synthesis
regulators: myostatin, growth hormone
what if I give someone who is deficient in growth hormone, growth hormones?
give GH to someone who is deficient in it this increases muscle mass!
what does myostatin do
negatively regulates muscle growth
if you delete or lose function in the myostatin gene. then muscle overgrowth occurs!
ex: super muscular dog!
Cross section of a muscle fascicle – nice figure (though satellite are cells not shown)
what is shown
fibroblast
motor neurons (axons)
capillaries
pericytes
perimysium
connective tissue
adipocytes
pericytes
cells present at intervals along the walls of capillaries
what if I injure skeletal muscle
-skeletal muscle Is multinucleate (has Many nuclei)
-wear and tear, there are mechanics to repair it
-injury to SKM causes SKM to die, causing a loss in muscle fibers
-if you lose muscle fiber (cell)
-then the remaining muscle fiber cells get bigger
-muscles are not mitotic
Satellite cells (stem cells) in sk muscle
they are located between the sarcolemma of a muscle fiber and the extracellular matrix (basal lamina).
Population is heterogenous (differ in gene expression, ability to differentiate, not all are necessarily true stem cells.)
why cells are needed for hypertrophy of SKM
satellite cells
info about satellite cells of SKM
they are stem cells
Upon stimulation from exercise or following muscle injury, satellite cells become activated and enter mitosis.
the satellite cells have their own nucleus, and go through mitosis
either asymmetric or symmetric division occurs
asymmetric division of satellite cells
the cell identical to the parent cell is on top and the different cell is on the bottom
the cell that is different, differentiates and fuses with the basal lamina of the muscle fiber to make the cell bigger. this causes there to be another nuclei present in the muscle fiber (called myonuclei). This is why a muscle fiber is multinucleate
fusion makes the muscle fiber bigger and adds nucleus
the muscle fiber itself cannot go through mitosis
symmetric division of satellite cells
both cells are side by side and they are identical to the parent cell and do not fuse into the basal lamina of the muscle fiber
Development in the womb of skm
Progenitor cells
Progenitor cells (= myoblasts) fuse to form myofibers
Post-birth and childhood of skm
of myofibers is constant, but each grows in size
This is accomplished by fusion of satellite cells
(satellite cells are postnatal stem cells)
Adulthood of skm
of myofibers is stable (as long as you have not been injured)
Occasional satellite cell fusion to repair wear and tear
Injury (Traumatic lesions or Genetic Defects)
of skm
Degeneration-Regeneration repair process
(events happening at the molecular level, cell level, and tissue level)
RELIES ON SATELLITE CELLS!
Degeneration of skm
Necrosis (unplanned cell death) of damaged muscle fiber
Inflammatory response
(blood vessels leak, fluid and cells move to injury site)
regeneration of skm
Activation, differentiation and fusion of satellite cells
Maturation and remodeling of newly formed fibers
costameres
Multiprotein complexes in striated muscles
function of costameres
Link the sarcomeres to the sarcolemma, coordinate contraction with sarcolemma and extracellular matrix (ECM)
Transmit forces from the sarcomere to the ECM and from the ECM to the sarcomere
Maintain sarcolemma integrity
Proteins within the costamere:
Vinculin-Talin-Integrin Complex
&
Dystrophin glycoprotein complex (also called DAG complex)
Vinculin-Talin-Integrin Complex
Integrins are transmembrane proteins
ECM components bind to integrins
Dystrophin glycoprotein complex (also called DAG complex)
This includes dystrophin, dystrophin-associated glycoprotein and others
Dystrophin is the protein that is mutated in muscular dystrophy (DMD, Becker’s, types of muscular dystrophy)- DYS = something is wrong
muscular dystrophy
-loss of skm mass and is replaced with fat and connective tissue
DMD = Duchenne muscular dystrophy
Muscle atrophy (non-disease related)
Disuse Atrophy- Decrease in myofiber size only.
Sarcopenia (age-related)
-Decrease in myofiber size.
Also decrease in myofiber number.
Reduced/changed satellite cell function over time.
Regulators of muscle mass:
Muscle load
(e.g. mechanical stimulus)
Muscle neuron activity
Hormones, e.g:
Growth hormone (big in development)
Insulin
Insuling-like growth factors (IGFs)
Costameres
Regulate signaling
Integrate both mechanical and humoral stimuli
Humoral stimuli are concentrations of compounds (like ions, glucose) in the blood or extracellular fluid
Changes in these concentrations can trigger hormone secretion
how do you coordinate muscle movement
upper motor neurons of the CNS are involved in planning and talk to:
lower motor neurons: PNS which have cell bodies in the spinal cord that connect with SKM (motor neurons in motor unit)
The Big Picture of Control of Movement by the Nervous System.
1- CNS: upper motor neurons in the premotor cortex select a motor program. the primayr motor cortex is involved in planning movement
2- the basal nuclei enable the thalamus to stimulate upper motor neurons of the primary motor cortex
3- CNS to PNS: upper motor neurons stimulate lower motor neurons
4- PNS: lower motor neurons stimulate a SKM to contract
5- PNS to CNS: Sensory information is relayed back
to the cerebellum in the CNS. The cerebellum
sends instructions to upper motor neurons to
modify movement as needed
(cerebellum need for Smooth Muscle movement)
Reflex Arcs
Integration of Sensory and Motor Function
1- sensory (afferent) division, PNS detects and delivers
stimulus to CNS.
2- CNS integrates stimulus.
3- PNS delivers motor response
from CNS to effectors.
A simple stretch reflex.
1- An external force stretches the muscle.
2- Muscle spindles detect the stretch, and sensory afferents transmit an action potential to the spinal cord.
3- In the spinal cord,
sensory afferents
synapse on motor
neurons and trigger
an action potential.
4-motor neurons
stimulate the muscle to
contract, and it returns
to its optimal length
The flexion and crossed-extension reflexes.
1- When stimulated,
nociceptive
Afferents transmit
the painful
stimulus to the
spinal cord.
2-Motor
neurons
stimulate
muscles that
flex the limb
receiving the
painful
stimulus.
3-Motor neurons
stimulate muscles
that extend the
opposite limb to
maintain balance.
two types of paralysis
flaccid paralysis (ALS) & spastic paralysis
flaccid paralysis (ALS)
damage to the spinal cord (@ the place where motor neurons would exit) affects the lower motor neurons
results in no ACH to the muscle, which results in no impulses, which results in no voluntary or involuntary muscle movement
about toxins: can cause paralysis by messing with ACH
spastic paralysis
damage to the primary motor cortex (damage to upper motor neurons)
spinal motor neurons (lower motor neurons) still function
results in no voluntary movement; but can still have involuntary movement
diuresis
kidneys filter top much, bodily fluid; body makes extra pee when need to get rid of something/substance
hyperkalemia
high potassium in the blood
hypokalemia
low potassium in the blood
idiopathic
disease of unknown origin
iatrogenic
caused by the doctor (treatment)
ex: Cushing’s disease or disorder- increased cortisol has significant effects: on weight, nutrient use, adipose distribution
in Cushing’s disease, cortisol as medicine modifies the immune system
nutrient helps with what
help cells make ATP or macromolecule
ex: glucose, fatty acid
minerals don’t help with what
don’t help make ATP, important for cell function
muscle force
of AP/time + recruitment, size of muscle fiber
muscle speed
fast twitch + slow twitch, speed of myosin head
cells have ATP available always. Source of ATP depends on type of exercise
melatonin
peaks at night, low in morning
