Module 3 - Neural and Hormonal Communication Flashcards
(121 cards)
1
Q
List the 4 types of chemical messengers
A
Neurohormones, hormones, neurotransmitters, paracrines
2
Q
Differentiate between hormones and neurohormones
A
Hormones are compounds released by secretory cells directly into the blood stream, where they travel to a distant target to have an effect.
Neurohormones are released into the blood by neurosecretory neurons and they function as hormones
3
Q
What are gap junctions?
A
• Small ions and molecules are directly exchanged between interacting cells without interacting with the ECF
4
Q
What are surface proteins?
A
- Act as identifying markers
* Allows phagocytes to destroy any undesirable, non-self cells
5
Q
What are extracellular chemical messengers?
A
- Synthesized by specialized cells to accomplish a specific goal
- Messenger binds to receptors on target cells, specific to each messenger
6
Q
What are the 4 different extracellular chemical messengers?
A
Paracrines
Neurotransmitters
Hormones
Neurohormones
7
Q
What are paracrines?
A
- Local chemical messengers for effects on neighbouring cells
- Must be released to accomplish a specific goal
- Distributed by simple diffusion
8
Q
What is an example of a paracrine that is related to inflammatory responses?
A
Histamines
9
Q
What are neurotransmitters?
A
- How neurons communicate with their target cells that include neurons, muscle, or gland
- Short range in response to electrical signals
- Diffuse into a small ECF space
10
Q
What are hormones?
A
- Long range messengers secreted into blood by endocrine glands in response to a signal
- Carried throughout the body to their target cells
- Non target cells do not have receptors for the hormone, so it has no effect on them
11
Q
What are neurohormones?
A
• Hormones released into blood by neurosecretory neurons
o Release its chemical messenger in response to enervation
• Carried throughout the body to their target cells
12
Q
What is signal transduction?
A
- Process of incoming signals conveyed to target cells interior for execution
- May pass through plasma membrane or need to bind to a surface protein for transport
13
Q
What are the two general responses for first messengers?
A
o Opening or closing channels
o Activating second-messenger systems
14
Q
What is a transducer?
A
• Device receiving energy from one system and transmits it into a different for to another system
15
Q
What are chemically gates channels and how do they work?
A
- Opening or closing specific channels
- Results in short term movement of ions into or out of the cell
- Important to nerve and muscle physiology
- Once action is complete, messenger is removed from receptor site, and channels revert to original position
16
Q
What are second messenger pathways?
A
- First messenger binds to receptor site on the membrane
- Activates a second messenger that is inside the cell which then relays the orders to particular intracellular proteins to carry out the desired response
- Diverse responses is due to specialization of the cell, not the pathway used
17
Q
What are graded potentials?
A
• Local changes in membrane potential that occur in varying strength
o Most commonly Na+
• Produced when triggered and ion channels open in a specific area of the excitable cell membrane, strength of graded potential is related to strength of trigger
18
Q
What is the active area in a a graded potential and what will happen to it?
A
o Temporarily depolarized region
o Will move to inactive area as it continues to depolarize until
Runs out of strength and repolarizes
Reaches the threshold level and depolarizes the cell
19
Q
What is current?
A
o Any flow of electrical charges
20
Q
What is resistance and how does this affect the graded potential?
A
o Hinderance to electrical charge movement
o Lipid bilayer is a good insulator
o Current carried by ions can only move through ion channels
21
Q
What is an action potential?
A
- The actual firing of a neuron
- Actuated by voltage gates which only open after a certain voltage has been reached and allows ions (Na+ and K+) to move down the gradient
- Cell becomes temporarily more positive inside than outside
- Travels undiminished throughout the entire cell membrane
22
Q
What is the resting potential?
A
- “Resting” occurs when the neuron is not firing
- The potential is in the difference in the charge between the inside and outside of the cell
- On average it is -70 mV but different for every neuron
23
Q
How is the resting potential of -70 mV maintained?
A
• There are no negative ions involved, but there are more positive ions outside the cell than inside the cell, resulting in relative negativity
o There are more positive sodium ions moving out of the cell than positive potassium ions moving in
o This resting membrane potential sets the nerve up to be able to send electrical signals
• Voltage gated channels closed
• Na+/K+ pump works to keep the ions in their proper position in the long run
24
Q
How does the sodium/potassium pump work?
A
- 3 Na+ from inside the cell enter the carrier protein
- ATP is split, the Phosphate group stays with the carrier protein and ADP is released as a by product
- The Na+ is moved out of the cell against the concentration gradient
- A change in the carrier protein occurs with it still facing the outside of the cell
- 2 K+ from outside the cell enter the carrier protein
- The K+ is moved into the cell against the concentration gradient
- The phosphate group is released and the carrier protein returns to it’s original state of ready for 3 Na+ ions and another ATP molecule
- This establishes the resting potential as 3 Na+ ions out and 2 K+ ions in resulting in a more positive charge outside the cell than inside the cell
25
Other than the sodium/potassium pump, what are other contributors to the negative interior or the cell?
• Fixed negative ions (anion) that cannot leave the cell as they are too large
o While they contribute to the overall resting potential, they do not contribute to the action potential and firing of the nerve as they cannot move
• Leak channels
o Allow for some movement of both Na+ and K+ via diffusion
Na+ wants to enter the cell
K+ want to leave the cell
o More K+ channels than Na+ channels further increasing the difference in charge
o While this does contribute minorly, it is a slow process and isn’t enough on its own
26
What are leak channels?
• Leak channels
o Allow for some movement of both Na+ and K+ via diffusion
Na+ wants to enter the cell
K+ want to leave the cell
o More K+ channels than Na+ channels further increasing the difference in charge
o While this does contribute minorly to resting potential, it is a slow process and isn’t enough on its own
27
What are the 2 gates that sodium channels have and how do they work?
Activation Gate
• Guards channel by opening/closing like a hinged door
Inactivation Gate
• Ball and chain made of amino acids
• Open when ball is dangling free on its chain
• Closed when ball binds to receptor located at channel opening effectively blocking it
28
What are the different conformations of the Na+ channels?
Open, or Activated
• Both activation and inactivation gates are open
• Rapid opening triggered at threshold
Closed but Capable of Opening
• Activation gate closed, but inactivation gate open
Closed and Not Capable of Opening or Inactivated
• Activation gate open and inactivation gate closed
• Slow closing triggered at threshold
29
Compare the K+ channels with Na+ channels.
* Have the same 3 conformations, open, closed, or inactivated
* Each consists of 4 separate subunits so no distinct activation/inactivation gates
* Modifications to subunits altering conformation is made by changes in the electrical field
30
What is an action potential?
* The actual firing of a neuron
* Actuated by voltage gates which only open after a certain voltage has been reached and allows ions (Na+ and K+) to move down the gradient
* Cell becomes temporarily more positive inside than outside
* Travels undiminished throughout the entire cell membrane
* About 1 in the 100 000 Na+ and K+ ions so the cell is capable of depolarizing multiple times without dramatic change in concentrations
31
What is receptor activation and what types are there?
• Dendrites receive information
Inhibitory
Hyperpolarizing signals
Moving in a more negative direction from the resting membrane
Cell will return to resting membrane
Excitatory
Depolarizing signals
Some Na+ voltage gated channels open
Moving in a more positive direction from the resting membrane
32
What are graded potentials?
• Local changes in membrane potential that occur in varying strength
o Most commonly Na+
• Produced when triggered and ion channels open in a specific area of the excitable cell membrane, strength of graded potential is related to strength of trigger
33
What is the active area of a graded potential?
o Temporarily depolarized region
o Will move to inactive area as it continues to depolarize until
Runs out of strength and repolarizes
Reaches the threshold level and depolarizes the cell
34
What is current?
o Any flow of electrical charges
35
What is resistance?
o Hinderance to electrical charge movement
o Lipid bilayer is a good insulator
o Current carried by ions can only move through ion channels
36
What is the threshold?
* Minimum depolarization to trigger the “all or nothing” response
* If the depolarization is not strong enough to reach the threshold limit, the cell will return to resting membrane
* Once the threshold is reached, it triggers depolarization
37
What happens during depolarization?
• Voltage gated sodium channels open
o Na+ rushes from outside the cell to inside the cell
o Creates a very fast spike of the + charge rushing in
o The peak point of this spike, at about +30 mV, equilibrium potential reached
Permeability to sodium (PNA+) starts to fall
Triggers repolarization
38
What occurs during repolarization?
• Sodium channels become inactivated
o Closing is slow (0.5 milliseconds) and is actually triggered at the same time that it opens
o The delay is what allows depolarization
o Remains inactivated until voltage goes back to resting -70 mV
• Voltage gated potassium channels open
o Actually triggered during threshold but is slow to open so depolarization occurs first
o K+ ions flow out of the cell
o Decreases the positive charge within the membrane
• Once back down to threshold levels, potassium gates start to close
39
What is hyperpolarization?
* Also called overshoot
* The charge drops lower than the resting membrane charge
* Occurs because the potassium gates are slow close and a little more K+ leaks out than needed
40
What is the refractory period?
* Inability for a new action potential immediately following depolarization
* Prevents action potential from traveling backwards up the axon
* Result of the changing status of the Na+ and K+ voltage gated channels
* Sets limits on max number during any one period of time
* Different refractory rates for different types of neurons
41
What are the two components of the refractory period?
Absolute and relative refractory period
42
What is the absolute refractory period?
* Once Na+ channels are triggered open, the inactive conformation has also been triggered
* Inactive conformation lasts until resting potential is restored and they are closed by can be opened again
43
What is the relative refractory period?
• Follows absolute refractory period
• Result of slow closing Na+ and K+ voltage gated channels
o Fewer Na+ to depolarize with a new action potential
• Action potential can be produced but triggering event must be must stronger than usual
• Depending on number of available Na+ voltage channels available, the action potentials amplitude may be lower than normal
44
How does the body know that one stimulus is stronger than another?
• Stronger stimulus fires more action potentials, either in frequency or number or neurons firing, not a stronger depolarization
45
How do unmyelinated neurons transmit the impulses down the nerve cell?
• Contiguous conduction
o Action potential spread along every patch of membrane down the length of the axon
• Depolarization starts in the dendrites
• Positive charge moves down the axon, continuing to set off the depolarization down the axon
o Sodium diffuses down the axon because there is little sodium there due to Na+/K+ pump
• Repolarization and movement of potassium follows
46
How do Myelinated Neurons transmit an impulse down the nerve, what parts are there and what are their roles?
• Saltatory conduction
o The action potential “jumps” from node to node
o Moves impulse ~ 50 times faster than contiguous conduction
Myelin
• Primarily lipids so act as an insulator preventing ion movement
• Formed by oligodendrocytes in the CNS
• Formed by the Schwann cells in the PNS
Nodes of Ranvier
• Located between myelinated regions
• Axonal membrane is exposed to ECF
• Site of the only voltage gated channels
• These gaps are important as they are needed to refresh the Na+ ions to keep the action potential going
• Sodium ions re-enter the neuron and then diffuse within the neuron to areas of low sodium concentration, depolarizing and triggering sodium voltage-gated ion channels further down the neuron
• The diffusion process is less time-consuming than waiting for voltage-gated ion channels all along the neuron
47
How does a larger diameter affect the speed of a neuron?
o The larger the diameter of a neuron axon, the less resistance, and therefore, the faster the flow
48
What are dendrites and what do they do?
* Considered the input zone
* Usually branched in appearance that detect stimuli
* Dendritic spines are receptor sites for chemical messengers
* Take impulse to the cell body
* Cytoplasm contains Nissl bodies, mitochondria, and other organelles
49
What is the cell body?
* Also called a soma
| * Round shape that contains the nucleus and other organelles
50
What is the axon hillock?
o Considered the trigger zone for the axon
o Cone-shaped elevation where the axon arises from the soma
o Greatest density of sodium voltage gated channels making it easily excitable
51
What are axons?
• Also called a nerve fiber
o Is a general term for any neuronal process that emerges from the cell body but often only references the axon
• Considered the conducting zone
• Conduct the impulse away from the cell body
• Long, thin, cylindrical projection
• May have some branching at the distal portion
• Interacts with another neuron, muscle fiber, or gland
52
What are axon collaterals?
side branches usually at right angles to the axon
53
What is the axon terminal?
o Considered the output zone
o End of the axon
o Highly branched
o Releases chemical messengers to influence other cells
54
What are oligodendrocytes and do they allow for regeneration?
• Resemble astrocytes but smaller with fewer processes
• Processes responsible for the myelin sheath in CNS
• Do not possess regenerative properties
• Synthesize proteins to prevent axon growth
o May serve to keep axons from growing where they shouldn’t
55
What are Schwann cells and do they allow for regeneration?
• Also called neurolemmocytes
• Flat cells that encircle PNS axons
• Forms myelin sheaths in PNS
• Can enclose multiple unmyelinated axons
• Participate in axon regeneration
o Phagocytize debris left from the degeneration of the axon that is cut from the cell body
o Remain after to form a regeneration tube
Guides new materials to proper destination
o Secretes chemicals that the remaining axon connected to the cell body uses to “sniff” its way down the regeneration tube
56
What happens at the synapse during an action potential?
* Presynaptic neuron conducts action potential towards the synapse
* Depolarization of the axon terminal causes voltage gated calcium channels in the synaptic knob to open
* Ca2+ flows into the synaptic knob
* Calcium triggers fusion of neurotransmitter vesicles with the membrane (exocytosis)
* Neurotransmitters are released into the synaptic cleft and diffuse across
* Bind to protein receptors on the subsynaptic membrane of the postsynaptic neuron
57
What is postsynaptic potential?
* Change in voltage created when neurotransmitters bind to receptor sites on the post synaptic cell which can be excitatory or inhibitory
* Post synaptic neuron takes into
* If enough of a change in potential is reached (threshold level), an action potential is created
58
What is EPSP?
Excitatory Postsynaptic Potential (EPSP)
• Neurotransmitter binding to the subsynaptic membrane increases permeability to Na+ and K+ simultaneously
• Lots of Na+ flows inwards while only a little K+ flows outwards
• Causes net flow of positive ions in, resulting in small depolarization of postsynaptic neuron
o Brings it closer to threshold but not usually enough to reach it with a single synapse
59
What is IPSP?
Inhibitory Postsynaptic Potential (IPSP)
• Neurotransmitter binding to the subsynaptic membrane increases permeability to K+ or Cl-
• K+ flows out or CL- flows in, results in slightly negative charge in the postsynaptic neuron
• Produces small hyperpolarization
o Pulls it further from threshold
60
What is grand postsynaptic potential?
Grand Postsynaptic Potential (GPSP)
• Sum total of all EPSPs and IPSPs occurring at about the same time
• Determines if the neuron will have an action potential based on input
61
What are the two types of GPSP?
Temporal summation and spatial summation
62
What is temporal summation?
* Reaching threshold by rapid, repetitive excitation from a single persistent input
* With IPSPs, postsynaptic membrane moves further away from threshold
63
What is spatial summation?
* Reaching threshold by concurrent activation of several excitatory inputs
* With IPSPs, postsynaptic membrane moves further away from threshold
64
How do EPSPs and IPSPs work together?
* EPSPs and IPSPs cancel each other out
| * Extent of cancellation depends on respective magnitudes
65
What are neurotransmitters?
* About 100 substances are either known or suspected to be neurotransmitters
* Located in the axon terminal, the end of the presynaptic (or originating) neuron
* Usually stored in packages called synaptic vesicles
* Can be excitatory or inhibitory
* Common for mature neurons to have one small-molecule transmitter and one or more peptides working synergistically on the same target cells
* May release multiple neurotransmitters
66
What are neuropeptides?
* Larger than neurotransmitters and made of 2-40 amino acids
* Built in the ER or Golgi body and then transferred down to the axon terminal via the microtubular highways
* Stored in large dense – core vesicles
* Ca2+ induces exocytosis at the same time as neurotransmitters
* An axon may release one or more neuropeptides with the neurotransmitter
* Have slower, more prolonged action than the neurotransmitter
* May function as a neurotransmitter or a neuromodulator
67
What is a neuromodulator?
* Chemical messengers that do not cause the formation of EPSPs or IPSPs or
* Bring about long-term changes that enhance or depress the action of the synapse
* May bind to receptors on either the pre or post synaptic neuron
* Can work in multiple places with a variety of reactions
68
What is presynaptic modularization?
• A modulatory neuron synapses with the presynaptic neuron and alters the amount of neurotransmitter released from the presynaptic terminal
69
What is presynaptic inhibition?
* Transmitter released from the presynaptic neuron is diminished when the modulatory terminal also fires
* Reduces amount of Ca2+ that enters the presynaptic neuron so less is available to bind to neurotransmitter vesicles
* Only affects an individual presynaptic neuron so more selective than IPSPs that work on the entire membrane
70
What is presynaptic facilitation?
Transmitter released from the presynaptic neuron is enhanced when the modulatory terminal also fires
71
What is convergence?
* A neuron that has other neurons synapsing on it
| * Allows a single cell to be influenced by thousands of other cells
72
What is divergence?
* Branching of axon terminals with a synapse at the end of each branch
* Allows a single cell to influence many other cells
73
Which one of the following ions is the most permeable in a resting nerve cell?
a) anions
b) calcium
c) potassium
d) sodium
C
74
What is hyperpolarization?
The membrane potential becoming more negative than the resting membrane potential
75
What is the rising phase of an action potential is caused by?
Sodium influx
76
Neurotransmitters are released from presynaptic neurons by the influx of what ion?
calcium
77
Hyperpolarization of the postsynaptic cell is called
a) excitatory postsynaptic potential
b) inhibitory postsynaptic potential
c) grand postsynaptic potential
d) summation
B
78
Define resting membrane potential
The unequal charge between inside the cell membrane and outside the cell membrane that allows for an action potential
79
List the four types of gated channels
Chemically gated, voltage gated, mechanically gated, and thermally gated channels
80
What is a refractory period?
The time after an action potential in which the neuron is unable to be stimulated again by normal events
81
What is the synaptic cleft?
The very small space between the presynaptic and postsynaptic neuron
82
Explain why action potentials are initiated in the axon hillock
In the axon hillock, the density of voltage-gated Na+ channels is the greatest, which makes this area more sensitive to membrane depolarization
83
Implementing your knowledge of the Nernst equation, which of the following parameters is MOST important for determining equilibrium potential?
a) The Faraday constant
b) Ion concentrations
c) Ion valence
d) The universal gas constant
B
84
When compared to action potentials, which one of the following is a distinguishing characteristic of graded potentials?
a) They are all-or-none
b) They are of constant magnitude
c) They do not decay as they spread from the triggering event area
d) They are proportional to the stimulus
D
85
Applying your knowledge of voltage-gated ion channels, which ion channel state determines one way propagation in axons?
a) Active
b) Closed
c) Inactive
d) Resting
C
86
Neurons have four functional zones, the output zone is the part where
a) Incoming signals are received
b) Action potentials are initiated
c) Action potentials are conducted
d) Chemical messengers are released
D
87
Which is the following neurons would have the greatest conduction velocity?
a) Small diameter, unmyelinated
b) Large diameter, unmyelinated
c) Small diameter, myelinated
d) Large diameter, myelinated
D
88
Distinguish between polarization, depolarization, and hyperpolarization
Polarization - Electrical potential caused by the distribution of charges across the plasma membrane
Depolarization - When the electrical potential becomes more positive
Hyperpolarization - When the electrical potential becomes more negative
89
Compare the events that occur at excitatory and inhibitory synapses
Excitatory synapses causes small depolarization in the postsynaptic cell
Inhibitory synapses cause small hyperpolarization in the postsynaptic cell
90
Distinguish between temporal summation and spatial summation
Temporal summation - multiple firings from the same presynaptic neuron to bring postsynaptic neuron to threshold
Spatial summation - firing from multiple presynaptic neurons simultaneously to bring postsynaptic neuron to threshold
91
Compare and contrast the roles of Schwann cells and oligodendrocytes in neuronal regeneration
Schwann cells are found on peripheral nerves. When an axon is cut, the axon on the nerve terminal side of the cut degenerates and is absorbed by the Schwann cells. The Schwann cells remain in the same tubular shape and provide a pathway for the regenerating axon.
Oligodendrocytes, which myelinate nerves in the CNS, do not promote axonal regeneration and actually secrete factors that inhibit nerve growth
92
Distinguish between absolute and relative refractory periods
Absolute refractory period - neuron unable to be triggered, regardless of the strength of the stimulus
Relative refractory period - neuron able to be triggered if the stimulus is considerably stronger than normal
93
What effect will adding more K+ to the outside of a cell have on membrane potential?
a) No effect
b) Depolarization
c) Hyperpolarization
d) Repolarization
B
94
If you were to decrease the resistance to current flow in an axon, what would be the effect?
a) Graded potentials would propagate further
b) Graded potentials would propagate less
c) There would be a greater loss of charge
d) There would be no loss of charge
A
95
Increasing the distance between nodes of Ranvier would have what effect on the propagation of an action potential down a myelinated axon?
a) No effect
b) An increase in conduction speed
c) A decrease in conduction speed
d) May block conduction
D
96
What happens when there is an increased amount of GABA released from a presynaptic neuron?
a) No change in the actions of GABA
b) A greater depolarization of the postsynaptic membrane
c) A greater hyperpolarization of the postsynaptic membrane
d) Triggering of an action potential in the postsynaptic neuron
C
97
Predict what happens when there is an increase in IPSP input
a) The postsynaptic neuron is brought to threshold
b) The grand postsynaptic potential is increased
c) An equal amount of EPSP is increased to compensate
d) It depends on how much EPSP input there is
D
98
Conjecture what would happen if a neuron was simultaneously stimulated at both ends
If a neuron were capable of being stimulated on both sides, the action potentials would meet in the middle of the axon. The two adjacent patches of the membrane in the middle would be in a refractory period, so further propagation of either action potential would be impossible.
99
Assume you touched a hot stove with your finger. Contraction of the biceps muscle causes flexion (bending) of the elbow, whereas contraction of the triceps muscle causes extension (straightening) of the elbow. What patter of postsynaptic potentials would be initiated as a reflex in the cell bodies of the neurons controlling these muscles to pull your hand away from the painful stimulus?
IPSPs would be sent to the triceps muscle to inhibit its actions and EPSPs would be sent to the biceps muscle to cause it to contract and pull your hand away
100
Your finger is being pricked to obtain a blood sample, which would initiate a withdrawal reflex. Contraction of the biceps muscle causes flexion (bending) of the elbow, whereas contraction of the triceps muscle causes extension (straightening) of the elbow. What pattern of postsynaptic potentials would you voluntarily produce in the neurons controlling the biceps and triceps to keep your arm extended in spite of the painful stimulus.
IPSPs would be sent to the biceps and EPSPs would be sent to the triceps to keep the arm extended
101
Assume presynaptic excitatory neuron A terminates on a postsynaptic cell near the axon hillock, and presynaptic excitatory neuron B terminates on the same postsynaptic cell on a dendrite located on the side of the cell body opposite the axon hillock. Explain why rapid firing of presynaptic neuron A could bring the postsynaptic neuron to threshold through temporal summation, thus initiating an action potential, whereas firing of presynaptic neuron B at the same frequency and the same magnitude of the EPSPs may not bring the postsynaptic neuron to threshold.
Presynaptic neurons work on a graded potential going to the axon hillock. The further from the hillock, the more the strength is lost before reaching the hillock, which would initiate the all-or-none response in the axon
102
How would neuronal activity be affected if voltage-gated sodium channels only existed in either the open or the closed states?
Neuronal activity would be profoundly disrupted because, without the inactivated state of sodium channels, there would be no one-way propagation of action potentials
103
Benjamin S. was diagnosed with hypertension and was advised by his doctor to monitor his salt intake to ensure that it was within the daily recommended levels. However, after reading more about how salt can cause hypertension, he decided to dramatically reduce salt from his diet. Following the abrupt change in his diet, he experienced symptoms such as confusion, short-term memory loss, fatigue, and muscle weakness as he developed hyponatremia. What would be an underlying cause of some of these symptoms?
During hyponatremia, there is a decrease in sodium in the blood, which would cause a decrease in sodium in the ECF. This alters both the chemical and electrical gradients from sodium across the plasma membrane. Neurons and other excitable cells can become harder to excite, which potentially could explain some of the neurological symptoms he was experiences.
104
What are hydrophilic hormones?
• Highly water soluble and low lipid solubility
• Amino acids arranged in a chain of varying length
o Peptides are short chains
o Proteins are long chains
105
What are lipophilic hormones?
• High lipid solubility and poor water solubility
• Thyroid hormones
o Iodinated tyrosine derivative
o Amine hormones
Include catecholamines and thyroid hormone
Have common tyrosine derivation
• Steroids
o Neutral lipids derived from cholesterol
o Includes adrenal and sex hormones
106
How are peptides synthesized, stored and secreted?
• Preprohormones, or precursor proteins, are synthesized by ribosomes on the rough ER, pinched off into vesicles, and migrates to the Golgi body
o Processed into active hormones
• Golgi body packages finished hormones into secretory vesicles which are stored in the cytoplasm
• When signalled, vesicles fuse with the membrane and are released via exocytosis into the blood stream
107
How are steroids synthesized, stored and secreted?
• Cholesterol is common precursor and stored in steroidogenic cells
• Produced through a series of enzymatic reactions
o Appropriate enzymes located only in tissues where the specific steroid is created
• Once produced, immediately diffuse across the membrane and into the blood stream
108
How are peptides transported through the body?
• Simply dissolved in plasma
109
How are steroids and thyroid hormones transported through the body?
• Majority bound to plasma proteins
o Some proteins are specific and other indiscriminatory to the hormones they transport
• Only the small, unbound, freely dissolved part of the hormone can cross the capillary wall and bind to a target cell receptor
o This part is the biologically active part
110
How are catecholamines transported through the body?
* About 50% circulate as free hormones
| * About 50% are loosely bound to the plasma protein albumin
111
Where is the site of receptor for hydrophilic hormones?
* Includes peptides and catecholamines
| * Bind with specific receptors on the outer plasma membrane of the target cell
112
Where is the site of receptor for lipophilic hormones?
* Including steroids and thyroid hormone
| * Pass easily through surface membrane to bind with specific receptors located inside the target cell
113
What are the 3 general means of action of hormones?
Change cells permeability
• Done by a few hydrophilic hormones
• Alters conformation of adjacent channel-forming proteins already in the membrane
Activate second-messenger system
• Done by most surface-binding hydrophilic hormones
• Alters activity of intracellular target proteins, usually enzymes for desired effect
```
Activating specific genes
• Done by all lipophilic hormones
• Cause formation of new intracellular proteins
o May be enzymatic or structural
o Produce desired effect
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114
How does the cAMP cycle work?
* Hormone (first messenger) binds to a surface membrane receptor of a G protein
* Unactivated G proteins consist of alpha, beta, and gamma subunits and when activated it releases the alpha subunit
* The released alpha subunit breaks away and moves along the inner surface of the membrane until it reaches an effector protein, adenylyl cyclase
* Adenylyl cyclase induces the conversion of ATP to cAMP by cleaving off 2 phosphates
* cAMP activates the protein kinase A enzyme
* Phosphorylates target protein changing its shape and function to either activating or inhibiting it bringing about the desired response
115
What does cAMP stand for?
cyclic adenosine monophosphate
116
How does the calcium second messenger system work?
• Hormone (first messenger) binds to a surface membrane receptor of a G protein
• Unactivated G proteins consist of alpha, beta, and gamma subunits and when activated it releases the alpha subunit
• The released alpha subunit breaks away and moves along the inner surface of the membrane until it reaches an effector protein, enzyme phospholipase C
• Breaks down phosphatidylinositol (PIP2)
o A component of the tails of the phospholipid molecules of the membrane
o Breaks down to 2 molecules that follow 2 paths
Inositol Triphosphate (IP3)
• Responsible for mobilizing intracellular Ca2+ stores to increase cytosolic Ca2+
• Calcium becomes second messenger and usually activates calmodulin
• Activates Ca2+ – calmodulin – dependent protein kinase
• Phosphorylates target protein changing its shape and function to either activating or inhibiting it bringing about the desired response
Diacylglycerol (DAG)
• Activates protein kinase C (PKC)
• Phosphorylates target protein changing its shape and function to either activating or inhibiting it bringing about the desired response
117
How is the response for a second messenger system inactivated?
• Once response is accomplished the response is terminated by
o First messenger is removed
o Alpha subunit rejoins bets and gamma subunits to restore G protein complex
o cAMP and other participating chemicals inactivated
118
How doe the cAMP and calcium pathways interact?
* Frequently overlap and influence each other
* Calmodulin influences cAMP
* Protein kinase A may change activity of Ca2+ channels or carriers
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How are second messenger pathways amplified?
* Can be accomplished by a cascade of events
| * Allows a small concentration of hormones and other chemical messengers to trigger significant cell responses
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How are second messenger pathways modified?
• Accomplished through regulation of the number of surface proteins
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How do lipophilic hormones activate protein response?
• Free steroids or thyroid hormones not bound to a carrier diffuse through plasma membrane of target cell
• Binds to specific receptor which may be in the cytoplasm or within nucleus depending on hormone
• Hormone-receptor complex then binds with DNA at a attachment site called the hormone response element (HRE)
o Each receptor type binds with different HREs
• Turns on a specific gene which contains a code for synthesizing protein which is then transcribed into mRNA
• mRNA binds to a ribosome in the cytoplasm and synthesizes a new protein
• New protein, enzymatic or structural, produces the desired response
