Autonomic Nervous System - Apex Flashcards
Examples of positive feedback control in the human body include: (Select 3).:
a. generation of an AP
b. PaCO2 regulation
c. coagulation cascade
d. core temperature
e. serum glucose concentration
f. childbirth
A, F, and C
Homeostasis is a steady-state condition that comes with a price - it requires ____ to maintain the system.
energy
What does a negative feedback system dO?
Reverse a disturbance in some factors and leads to stability
What does a positive feedback system do?
Enhances or accelerates a disturbance in some factors and usually leads to instability
Any physiologic system that needs to be maintained in a normal range (set point) requires a ____.
control system
What four things must a control system be able to do:
- sense the regulated variable
- compare the input signal with an internal reference/set point
- Multiply the error signal by a proportionality coefficient (the gain) to produce an output signal
- adjust the important factor by activating an effector system
What is the most common control system for maintaining homeostasis?
A closed negative feedback loop
What are the sensors for the regulated variable - PaCO2?
central chemoreceptors
CO2 is hydrated in the ____, forming ____ which spontaneously dissociates into ___ and ___.
CSF; H2CO3; H+ and HCO3-
The PaCO2 is directly reflected by the ____, which is detected by central chemoreceptors in the _____ of the _____.
H+; retrotrapezoid nucleus of the medulla
What is the feedback controller for PaCO2?
Dorsal respiratory group (DRG)/central pattern generator (CPG)
What are the effectors for the regulated variable - PaCO2?
muscles of inspiration
An increased PaCO2 (the disturbance) results in a decreased PaCO2. What type of system is this?
A negative feedback control system
What is the sensor for the regulated variable - cervical opening?
Stretch receptors in the cervix
During L&D, sensory impulses from the stretch receptors in the cervix are sent to the _____.
hypothalamus
What is the feedback controller for the regulated variable - cervical opening?
The periventricular and supraoptic nuclei of the hypothalamus
Increased stretch impulses from the cervix received at the hypothalamus stimulate the _______ to release more _____.
posterior pituitary (neurohypophysis); oxytocin
What are the effectors for the regulated variable - cervical opening?
Oxytocin and the myometrium
Oxytocin binds to G protein-coupled receptors (Gq) on the _____, producing more ______.
myometrium; powerful uterine contractions
The fetus pushing more forcefully against the cervix and stimulating more oxytocin release is an example of which type of system?
Positive feedback cycle system
Oxytocin also stimulates _____ production by the uterine lining.
prostaglandin
Negative feedback or positive feedback??
Control of serum sodium concentration
Negative feedback
Negative feedback or positive feedback??
Enhances or accelerates a disturbance in a vital parameter
Positive feedback
Negative feedback or positive feedback??
Propagation of an AP
Positive feedback
Negative feedback or positive feedback??
Leads to stability in a vital parameter
Negative feedback
Negative feedback or positive feedback??
Leads to instability in a vital parameter
Positive feedback
Negative feedback or positive feedback??
Opposes or reverses a disturbance in a vital parameter
Negative feedback
Which method of cell signaling occurs when a cell responds to a chemical signaling molecule that the cell itself produced and secreted?
a. endocrine signaling
b. paracrine signaling
c. neurotransmitter signaling
d. autocrine signaling
D - autocrine signaling
What is the intracellular response to extracellular signals called?
Cell signaling/signal transduction
The conversion of info into a chemical change is called _____, a universal property of living cells.
signal transduction
Info arrives at cells in what 4 forms:
- Purely physical (energy)
- Chemical
- Cellular
- Extracellular matrix molecules
What are examples of purely physical/energy forms?
light, sound, heat, pressure, electricity
What are examples of chemicals?
NT, hormones, eicosanoids, drugs, toxins
What are examples of a cellular form of information arriving at cells?
Gap junctions
What are extracellular matrix molecule examples?
Collagen (think of PLT adhesion), integrins, laminin
What are the 3 main methods of intracellular communication?
- endocrine
- paracrine
- autocrine
Endocrine cell signaling = _________
a signaling molecule (i.e., a hormone) is secreted by an endocrine cell and transported through the circulation where it acts on a distant target cell
What is neuroendocrine signaling?
A specific type of endocrine signaling, where a neuron is the source of the hormone secreted into the blood
What is an example of neuroendocrine signaling?
The adrenal medulla releases epinephrine that binds to B1 receptors on the heart
What is paracrine signaling?
A chemical signaling molecule is released by one cell and acts locally to regulate the behavior of a neighboring cell
_____ cell signaling is a specific form of paracrine signaling.
Neurotransmitter
What is autocrine signaling?
A cell responds to a signaling molecule that it also produced.
NE binding to a presynaptic A2 receptor on the same nerve terminal that released NE is an example of what type of signaling?
Autocrine
What does autocoids mean?
Local hormone
Where are autocoids and paracrine hormones produced?
Locally
Autocoids and paracrine hormones are released in smaller or larger quantities than endocrine hormones?
Smaller
T/F: Autocoids and paracrine hormones are intended to act locally and are metabolized locally.
True
A chemical molecule that binds to a receptor and initiates a cellular response is called a:
a. second messenger
b. transducer
c. ligand
d. kinase
C - ligand
What does signal transduction exhibit?
specificity and sensitivity
amplification
integration
feedback
compartmentalization
desensitization
The flow of info in a signal transduction sequence follows _____ pathways.
Orderly
What are the 6 processes in signal transduction sequences?
- recognition
- transduction
- transmission
- modulation
- response
- termination
What are the 4 types of receptor-based signal transducers?
- transmembrane G protein-coupled receptors (GPCR)
- Transmembrane gated ion channels
- transmembrane enzyme-linked receptors
- Soluble nuclear (intracellular) receptors
______ is imparted by the cell-specific receptor and is mediated by the same kinds of weak, non-covalent forces the mediate enzyme-substrate interactions.
Specificity (selectivity)
Bonds ordered from weakest to strongest: ____ < _____ < ____ < ____ < _____
Van der Waals < hydrophobic < Hydrogen < ionic < covalent
When does amplification by enzyme cascade result?
When an enzyme associated with a signal receptor is activated, and in turn catalyzes the activation of many molecules of a second enzyme, which activates a third enzyme, and so on
What is integration?
The ability of a signal-transducing system to receive multiple signals and produce a unified response appropriate to the cell’s needs
Multiple components of signaling pathways are often brought together on _____ to increase their local concentration and effects.
Scaffold proteins
_____ are scaffolding proteins in addition to calcium channels.
Ryanodine receptors
When does desensitization occur?
When a signal is present continuously, desensitization of the receptor system results. (when the stimulus falls below a certain threshold, the system again becomes sensitive)
What is the general flow of info through G protein-coupled receptor signal transduction pathways?
1st messenger –> receptor –> effector –> 2nd messenger –> cellular response
The 1st step of signaling sequences is ____.
recognition of the signal by its receptor
All receptors are _____
proteins
A general term for any chemical that binds to a receptor is what?
Ligand (note - ligand immediately implies that there’s a receptor involved)
A ligand is also called what?
the first messenger
What initiates the signaling sequence?
Energy from the stimulus-receptor interaction causes a conformational change in the receptor and then initiates the signaling sequence
What is the second stage of the signaling sequence?
TRANSDUCTION of the extracellular message into an intracellular signal or 2nd messenger
The conformational change of a receptor triggers either _____ or causes the receptor to _____.
catalytic activity intrinsic to the receptor; interact with membrane or cytoplasmic enzymes
The final consequence of RECOGNITION + TRANSDUCTION is the generation of a _____ or the activation of a _____.
second messenger; catalytic cascade
What messengers are extracellular signals?
1st
What messengers are intracellular signals?
2nd
_____ are extracellular signals, ____ are intracellular signals.
1st messengers; 2nd messengers
What occurs are tranduction?
TRANSMISSION
What is transmission during the signal sequence?
The second messenger’s signal to the appropriate effector(s)
T/F: There are multiple pathways for signal transmission.
True
What are some key activities in signal transmission pathways?
- activation of kinases that add phosphates to proteins
- release or sequestration of intracellular ions
- regulation of metabolic processes
____ and _____ typically occur during transmission
Amplification and integration
What stage of the signaling sequence does amplification typically occur?
Transmission
What stage of the signaling sequence does integration typically occur?
Transmission
What occurs after transmission?
MODULATION of downstream chemicals
What are two common modulation/”on/off” events?
enzymatic phosphorylation or dephosphorylation
What occurs after modulation?
RESPONSE of the cell to the initial stimulus
What are the different types of responses?
proliferation, differentiation, cell movement, metabolism, cell behavior
What occurs after the response stage of the signal sequence?
TERMINATION of the response
How is termination often accomplished?
feedback control
What is ATP?
adenosine triphosphate
What is IP3
Inositol triphosphate
Phenylephrine is a ____ for the ____ receptor.
ligand/agonist/first messenger; alpha-1
____ is a ligand for purinergic receptors.
ATP / adenosine
What is an example of a drug that has an extracellular target?
Dabigatran
What is an example of a drug that has an adhesion molecules?
Eptifibatide
ID the 4 categories of receptor-based signal transducers.
- G protein coupled receptors
- Gated ion channels
- Enzyme-linked receptors
- Soluble nuclear receptors
What is another name for a chemical that binds to a receptor?
ligand
What family of enzymes catalyzes the addition of a phosphate group to a molecule?
Kinases
What chemical messengers are derived from arachidonic acid? (select 3)
a. prostaglandins
b. thyroxine
c. aldosterone
d. leukotrienes
e. dopamine
f. anadamide
A - prostaglandins
D - leukotrienes
F - anandamide
Most chemical signals fall into 4 categories of molecules:
1. ______
2. ______
3. ______
4. ______
- small hydrophilic molecules
- lipophilic molecules
- peptides and proteins
- others
Where are small hydrophilic molecules, peptides, and protein messengers stored?
In vesicles inside the cells that synthesize these molecules
______, _____, ____, and _____ are molecules that are not stored in vesicles.
Lipophilic molecules, purine, gas, and endocannabinoid messengers
Chemical messenger molecules bind to either _____ receptors or ____ receptors.
cell-surface or intracellular (cytoplasmic or nuclear)
What are the small hydrophilic chemical messenger classes?
Amino acids
BIogenic amines
choline esters
iodothyronines
What are 4 examples of amino acids?
- glycine
- glutamate
- GABA (y-aminobutyric acid)
- aspartate
What are 5 examples of biogenic amines?
- dopamine
- norepineprhine
- epinephrine
- serotonin (5-HT)
- histamine
What is an example of choline esters?
acetylcholine
What are 2 examples of idothyronines?
- thyroxine (T4)
- triiodothyronine (T3)
Small hydrophilic molecules are polar molecules are are ____ at physiologic pH.
ionized.
Do small hydrophilic chemical messengers readily cross plasma membranes?
No - therefore needs cell-surface receptors
____ of an amino acid precursor is a theme.
Decarboxylation
What 4 things are derived from tyrosine?
- dopamine
- NE
- Epi
- iodothyronines
T/F: GABA and glutamate can be intercoverted.
True
How are small hydrophilic chemical messengers typically released?
exocytosis (exception is T3&T4)
T3 and T4 are released through a ____
transporter
What are the 3 types of lipophilic chemical messengers?
- steroids
- eicosanoids
- miscellaneous
Vitamin D3 and retinoids are _____ messengers.
Lipophilic (nonpolar)
Prostaglandins are _____
eicosanoids
Leukotrienes are _____
eicosanoids
Thromboxanes are _____
Eicosanoids
Steroids are derived from what?
cholesterol
How do steroids circulate in the blood?
bound to a protein
T/F: Steroids can diffuse through the lipid bilayer of plasma membranes.
True
Where do steroids to receptors of target cells?
in the cytoplasm or nucleus of target cells
What are eicosanoids derived from?
polyunsaturated fatty acids w/ 18, 20, and 22 carbons
_______ is the main precursor of eicosanoids.
Arachidonic acid (20 carbons)
Eicosanoids primarily have endocrine, autocrine, or paracrine actions?
autocrine and paracrine
T/F: Unlike steroids, eicosanoids usually bind to cell surface receptors.
True
What is calcitriol, 1,25-dihydroxycholecalciferol?
Vitamin D3
What is 1,25(OH)2D3?
Vitamin D3
______ is a cholesterol derivative but it does not retain the cholesterol ring structure.
Vitamin D3
Do steroids retain the cholesterol ring strucutre?
Yes
Retinoids are derived from what?
Vitamin A
Retinoids play a role in ______.
growth and development
Peptides and protein chemical messengers are generally ____ molecules.
hydrophilic (polar)
Peptides and protein chemical messengers do or do not readily cross plasma membranes?
Do not
How do peptides and protein chemical messengers circulate in the bloodstream?
As unbound molecules
____ and _____ are nucleotides and nucleosides.
ATP and Adenosine
Adeonsine and ATP are _____.
purines
T/F: Adenosine and ATP are stored in vesicles.
False
CO and NO are or are not lipid soluble?
Are
What kind of action do CO and NO have?
paracrine
What is NO synthesized from?
amino acid L-arginine
NO and CO serve as ____ neurotransmitters.
Retrograde
Anandamide (AEA) and 2-arachidonylgycerol (2-AG) are what type of chemical messengers?
Endocannabinoids
What are endocannabinoids derived from?
arachidonic acid
What receptors do endocannabinoids bind to?
CB-1 (CNS) and CB-2 (peripheral)
Endocannabinoids are lipophilic or hydrophilic?
Lipophilic
CB-1 and CB-2 are _____ receptors.
G protein-coupled
The brain has more _____ receptors than any other type of G protein-coupled recetpor!
cannabinoid
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Insulin - ___________
Peptide and protein molecules
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
NO - ___________
Lipophilic
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Angiotensin II - ___________
Peptide and protein
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Thyroxine - ___________
Hydrophilic
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Calcitriol - ___________
Lipophilic
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Substance P - ___________
Peptide and protein
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
GABA - ___________
Hydrophilic
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Aldosterone - ___________
Lipophilic
Small hydrophilic molecules, lipophilic molecules, or peptide and protein molecules???
Acetylcholine - ___________
Hydrophilic
Which categories of signaling molecules are stored in vesicles in the cell that synthesized the molecules?
- small hydrophilic chemical messengers
- peptide and protein chemical messengeres
Which lipophilic chemical messengers are not derived from cholesterol?
eicosanoids, retinoids, endocannabinoids
Dopamine, Epi, NE, and the idothyroinines are derived from which amino acid?
Tyrosine
How many times does a G protein-coupled receptor span the plasma membrane?
7
What is the largest and most diverse family of receptors on the cell surface?
G protein coupled receptors (GPCR)
What ligands bind to GPCRs?
NT, hormones, vasoactive peptides, odorants, tastants, and local chemical factors
About ___ to ___ of all drugs target GPCR.
1/2 to 2/3
G proteins are molecular switches and can _____ themselves through inherent GTPase activity in the ____ subunit.
inactivate; alpha
In the GPT-loaded state, the ____ interacts with downstream effects. What may also interact with downstream effectors?
alpha subunit; beta-gamma complex
What are the 4 G protein families?
- Gs (stimulatory)
- Gi (inhibitory)
- Gq
- G12,13
What does the following represent?
Ligand –> GPCR –> Effector –> 2nd messenger –> Cell Resposne
The sequence of signal transduction through GPCR
What 3 essential components characterize signal transduction through GPCRs?
- plasma membrane receptor with 7 transmembrane helical segments
- A guanosine nucleotide-binding protein (g protein) activates the effector enzyme/path
- An effector (usually enzyme) generates 2nd messenger
GPCRs have a plasma membrane receptor with _______ transmembrane ___ segments.
7; helical
(7-TM seven-helix or serpentine receptor)
What do G proteins link?
receptor activation with a variety of downstream effects
The ___ class of G proteins are associated with 7-TM receptors.
Heterotrimeric (αβᵞ subunits)
When are G proteins turned ON?
when a ligand binds to the receptor binding site
When are G proteins turned OFF?
By the intrinsic GTPase activity in the alpha subunit
GDP is bound to the ____ subunit.
alpha
When activated, the 𝜶βᵞ complex of GPRC disassembles into a free GTP bound ___ subunit and a separate ___ complex.
𝜶; βᵞ
A _____ will stimulate (or inhibit) the production of a second messenger that will ultimately produce a change in cellular function.
G𝜶 subunit
Major effector targets of G𝜶 subunits include: (3)
- adenylate cyclases (AC)
- Phospholipase C (PLC)
- Phospholipase A2 (PLA2)
T/F: The βᵞ complex can interact with down stream effectors.
True
What are major effector targets for Gβᵞ subunits? (3)
- Gi, 0-regulated potassium channels (GIRK)
- voltage-gated calcium channels
- beta-adrenergic receptor kinase (BARK)
The alpha subunit has intrinsic GTPase activity, which catalyzes the hydrolysis of GTP to ___ and ___.
GDP and Pi
Gs stimulates _____
adenylyl cyclase
Gi inhibits ____
adenylyl cyclase
Cq11 stimulates _____
phospholipase C (PLC)
C12,13 activates ______
small G proteins
____ toxin chemically alters the Gs subunit to inhibit the intrinsic GTPase activity.
Cholera
Cholera inhibits the intrinsic GTPase activity. What occurs because of this?
continuous activation of the G protein and adenylate cylcase –> cell is swamped with cAMP –> stimulation of the export of fluid across the intestinal epithelium
____ toxin chemically alters the Gi,0 subunit
Pertussis
McCune-Albright syndrome is characterized by defects of ______.
hormonal regulation
What causes McCune-Albright syndrome?
A gain-of-function mutation of Gs that correlates w/ a massive disturbance of Gs controlled. hormone production
What causes pseudohypoparathyroidism?
A loss-of-function mutation of Gs (results in effects of PTH being suppressed –> premature puberty w/ obesity, growth retardation, and skeletal deformities)
G-alpha subunit target effector OR G-beta/gamma subunit target effector???
Adenylyl cyclase
alpha
G-alpha subunit target effector OR G-beta/gamma subunit target effector???
Phospholipase C
alpha
G-alpha subunit target effector OR G-beta/gamma subunit target effector???
Voltage-gated Ca channels
beta/gamma
G-alpha subunit target effector OR G-beta/gamma subunit target effector???
Gi,0-regulated potassium channels
beta/gamma
G-alpha subunit target effector OR G-beta/gamma subunit target effector???
Phospholipase A2
alpha
G-alpha subunit target effector OR G-beta/gamma subunit target effector???
Beta-adrenergic receptor kinase
beta/gamma
Which heterotrimeric G-protein subunit contains the intrinsic GTPase activity?
alpha
Match each enzyme with the substrate –> second messenger reaction the enzyme catalyzes.
Phospholipase A2, Adenylyl Cyclase, and Phospholipase C
ATP –> cAMP
PIP2 –> IP3 + DAG
Phospholipid –> arachidonic acid
Phospholipase A2 + Phospholipid –> arachidonic acid
Adenylyl Cyclase + ATP –> cAMP
Phospholiapse C + PIP2 –> IP3 + DAG
GPCRs target what # of downstream effectors that produce second messengers?
3
Adenylyl cyclase —> ___________
cyclic adenosine monophostate (cAMP)
PHospholipase C (PLC) —> _________
inositol triphosphate (IP3) & diacylglycerol (DAG)
Phospholipase A2 (PLA2) –> ________
Eicosanoids (20-carbon lipid mediators)
T/F: Second messenger effects are tissue specific.
True
Second messenger effects are ____ specific.
tissue
____ plays a key role int he regulation of intracellular signal transduction.
cAMP
The intracellular effects of cAMP are mediated by the enzyme _________, ____.
cAMP-dependent protein kinase, PKA
_____ is a second messenger that leads to Ca2+ release from intracellular storage sites.
IP3 (inositol-1,4,5,-triphosphate)
Many downstream signaling events mediated by Ca2+ are modulated by a Ca2+ sensing and binding protein, _____.
calmodulin (CaM)
What is the function of adenylyl cyclase?
To convert ATP to cyclic adenosine monophosphate (cAMP)
IP3 and DAG are ____ messengers
second
___ together with ___ activates PLC
Gq,11 & Ca2+
IP3 binds to what channels and where?
Ca2+ channels on the endoplasmic reticulum
What is released after IP3 binds to a channel?
Calcium
DAG in the membrane acts as a docking site for and activator of _____.
protein kinase C (PKC)
Phospholipase A2 is a ___ dependent enzyme.
Ca2+
Phospholipase A2 liberates what from the cell membrane?
Arachidonic acid
Arachidonic acid is the precursor to how many families of lipid signaling. molecules?
3
What 3 lipid signaling molecules is arachidonic acid the precursor to?
- Prostaglandins and thromboxanes (porstanoids)
- Leukotrienes
- CYP450 monooxygenases
CYP450 monoxygenases catalyze the formation of ____ and ____ from the ____ substrace.
HETEs (hydroxyeicosatetraenoic acid); EET (cis-epoxyeicosatrienoic acid); arachidonic acid
Leukotrienes are generated when ___ encounters lipoxygenase.
arachidonic acid
Prostaglandins and thromboxanes are produced by the initial action of ____ on the arachidonic acid substrate.
cyxlooxygenases
Prostanoids, leukotrienes, HETEs, and EETs are collectively called _____.
Eicosanoids
In cardiac myocytes, increased cAMP does what?
enhances contractiliy
In cardiac myocytes, increased cAMP enhances contractility (____ receptors effects).
Beta-1
_____ messenger effects are tissue-specific.
Second
In smooth muscle of airways and vessels, increased cAMP causes _______.
relaxation and dilation.
In smooth muscle of airways and vessels, increased cAMP causes relaxation and dilation (_____ receptor effects).
Beta-2
In PLTs, increased cAMP _____.
reduces PLT aggregation
In principal cells of the nephron, increased cAMP ___________________.
promotes insertion of aquaporin-2 water channels in the apical membrane
Think of ____ as the sensors of second messengers.
protein kinases
What are kinases?
Enzymes that catalyze the addition of phosphate groups (PO4 -2) to their substrate
What are common tragets for kinases?
downstream proteins
_____ catalyze the removal of phosphate groups from their substrate.
Phophatases
cAMp activates ____ to modify cellular function.
protein kinase A (PKA)
Protein Kinase A (PKA) contains 2 _____ and 2 _____.
regulatory subunits; catalytic subunits
What happens when cAMP binds to the regulatory subunits of PKA?
It causes dissociation of the catalytic subunits
What are the catalytic subunits of PKA?
Serine/threonin (Ser/Thr) kinases
What terminates the action of cAMP?
Phosphodiesterases
What terminates the action of protein kinases?
Protein phosphatases
DAG is lipophilic or hydrophilic?
Lipophilic
DAG and Ca2+ activate what?
Protein Kinase C (PKC)
What cellular functions is PKC involved in? (its a lot….)
- receptor desensitization
- modulating membrane structure events
- regulating transcription
- mediating immune responses
- regulating cell growth
- learning and memory
When is the action of DAG terminated?
When the molecule is recycled into new phospholipids
IP3 is the ___ messenger that liberates ___ from intracellular storage sites.
second; Ca2+
Ca2+ is released from ER into the ____, resulting in a dramatic increase in intracellular or extracellular Calcium?
cytoplasm; intracellular
A high _____ activates several Ca2+ dependent protein kinases and phosphatases.
cytosolic [Ca2+]
Ca2+ signals are terminated by ATP-dependent processes:
1. ______________________
2. _______________________
Ca2+ is returned into the ER
Ca2+ is pumped out of the cell
When is the action of IP3 terminated?
when the molecule is recycled into new phophoslipids
Freely available intracellular Ca2+ is a ____ messenger.
2nd
_____ is directly or indirectly involved in most cell processes, from fertilization of the ovum to cell death.
Intracellular Ca2+
Unlike other second messengers, ____ is NOT synthesized, liberated from a precursor molecule, or activated by enzymes.
Calcium (it is the increased intracellular Ca2+ that is the signal)
What are the sources of Cytoplasmic Ca2+? (6)
- voltage-gated Ca channels
- storage- operated Ca channels
- nonselective TRP ion channels
- ionotropic NT receptors (NMDA)
- IP3-controlled Ca channels (ER)
- RyR Ca selective channels
Downstream Target of Ca2+:
Voltage-gated calcium channels - _____
proteins that buffer calcium - calmodulin and calsequestrin
Downstream Target of Ca2+:
storage-operated calcium channels - _____
Calcium sensor proteins (camodulin, troponin C, synaptotagmin [presynaptic vesicle exocytosis])
Downstream Target of Ca2+:
Nonselective TRP ion channels - _____
enzymes (PLA2, PKC, NO synthases)
Downstream Target of Ca2+:
Ionotropic NT receptors (NMDA) - _____
Receptors and ion channels: IP3 receptors, RyRs, Ca-activated K and Cl channels
Removal of cytoplasmic reticulum….
voltage-gated calcium channels = _________
Na+-Ca2+ Exchanger (NCX) at the plasma membrane
Removal of cytoplasmic reticulum….
storage-operated calcium channels = _________
Ca2+-ATPase (“pump”) at the plasma membrane (PMCA)
Removal of cytoplasmic reticulum….
Nonselective TRP ion channels = _________
Ca2+-ATPase at the sarcoplasmic (muscle) or endoplasmic reticulum (SERCAs)
What Ca2+ sending and binding protein modulates may downstream events mediated by Ca2+?
Calmodulin (CaM)
When intracellular Ca2+ concentration increases, _____ Ca2+ binds to CaM inducing a major conformation change to the protein.
3-4
The active Ca2+/CaM complex has a wide range of downstream targets including:
1.
2.
3.
4.
- NO synthase
- Ca2+/CaM dependent protein kinases (ex: myosin light-chain kinase)
- adenylyl cyclase
- cAMP-specific PDE
caMP, DAG, IP3, or iCa???
Lipid second messenger
DAG
caMP, DAG, IP3, or iCa???
Generated from PIP2 and stays in the plasma membrane
DAG
caMP, DAG, IP3, or iCa???
Targets ligand activated Ca channels on the ER
IP3
caMP, DAG, IP3, or iCa???
IP3 releases it from the ER
iCa
caMP, DAG, IP3, or iCa???
Removed from the cytoplasm by pumps and transporters
iCa
caMP, DAG, IP3, or iCa???
Generated from PIP2 and diffuses in the cytoplasm
IP3
caMP, DAG, IP3, or iCa???
Activates PKA
cAMP
caMP, DAG, IP3, or iCa???
Adenylyl cyclase catalyzes production
cAMP
caMP, DAG, IP3, or iCa???
ATP is the precursor
cAMP
Which G protein alpha subunit activates adenylyl cyclase?
G-alpha S activates adenylyl cyclase
Which 2 Ca transporters are found in the plasma membrane
- sodium-calcium exchanger (NCX)
- Ca2+ ATPase (pump, PMCA)
What enzyme family catalyzes the addition of a phosphate group to a substrate?
Kinases catalyze the addition of a phosphate group to their substrates
What enzyme produces IP3 and DAG from PIP2?
PLC (phopholipase C)
The 2 types of synpases in the human body are (select 2):
a. chemical
b. thermal
c. mechanical
d. electrical
A and D
_____ play a crucial role in AP and other electrical behavior of membranes.
Ion channels
Ion channels usually have what type of pores?
gated
What helps the nervous system get the right signal to the right place in the body at the right time?
An intercellular junction called the synpase
What are the two types of synapses?
electrical and chemical
____ synapses are far more prevalent and diverse.
Chemical
____ receptors are the key proteins of signal transduction at chemical synapses.
NT
NT receptors are transmembrane proteins that are either:
1. _____
2. _____
- ion channels (ionotropic receptors)
- coupled to heterotrimeric G proteins (metabotropic receptors)
____ synapses are polarized. What does this mean?
Chemical; primarily one-way communication
What are chemical synapses comprised of?
A presynaptic terminal, synaptic cleft, and postsynaptic membrane
What is the presynaptic terminal also called?
axon terminal, synaptic bouton, or synaptic knobs
How wide is the synaptic cleft on chemical synapses?
20-40 nm wide
Ion channels are integral membrane proteins that form ________ pores through which selected ions can pass.
water-filled pores
T/F: Ion channels exhibit ion selectivity.
True
What type of channels usually have gated pores?
Ion channels
What are the 3 different types of gated ion channels?
- voltage-gated (membrane)
- ligand-gated (chemical)
- Mechanically-gated (pressure/sensory receptors)
T/F: ALL ion channels are gated.
False - not all ion channels are gated
What is an example of an ion channel that is not gated?
“leaky” potassium channels that establish resting membrane potential
Chemical synapses convert a ____ signal ➡ a ____ signal through the release of NT.
electrical; chemical
Chemical synapses communicate messages in what direction?
one direction from the presynaptic membrane to the postsynaptic membrane, across the synaptic cleft
NT act as endocrine, paracrine, or autocrine messengers?
paracrine and autocrine messengers
NT act as 1st or 2nd messenger?
1st - they bind to receptors and generate electrical or biochemical signals in postsynaptic cells
What type of synapses allow bi-directional flow?
Electrical
At electrical synapses, cells are connected by what?
gap junctions
Gap junctions consist of 2 hemichannels called _____.
connexions
What allows the myocardial cells to depolarize synchronously?
intercalated discs in the heart that contain electrical synapses
All ionotropic receptors have ____ subunits whose arrangement defines a central pore.
4-5
When does ionotropic receptor activation cease?
When the NT dissociates from the receptor or when the receptor is desensitized
Ionotropic receptors participate in fast or slow synaptic responses?
Fast
What are metabotropic receptors?
7 transmembrane-spanning receptors coupled to heterotrimeric G proteins (GPCR)
Metabotropic receptors participate in ____responses compared to inotropic receptors.
slower (seconds to minutes); compared to milliseconds or faster
AChr, adrenergic receptors, GABAbR, opioid receptors, and 5-HT1R are all _____ receptors.
metabotropic
What receptors trigger biochemical cascade?
Metabotropic - tip it sounds like metabolism or metabolite… it activates enzymes
The presynaptic terminal of chemical synapses contain what 2 important organells?
Mitochondria
Synaptic vesicles
What is mitochondria’s job in presynaptic terminals?
provides ATP, biochemical intermediates, and enzymes for the syntehsis and degradation of NT
What is synaptic vesicles job in presynaptic terminals?
concentrate, store, and deliver NT at the synapse
Membrane depolarization causes _____ channels (N-type) to open, permitting Ca2+ ions to flow into the terminal.
Ca2+
Increased intracellular Ca2+ is sensed by _____ in the docking proteins complex. This triggers the fusion of vesicles with the presynaptic membrane. This process is _____.
synaptotagmin; exocytosis
NT molecules bind to either ____ or _____ receptors on the post-synaptic membrane, leading to a post-synaptic event.
ionotropic or metabotropic
Volatile anesthetics inhibit excitatory neurotransmission (via ___ and ____ receptors).
NMDA and nicotinic ACh
Volatile anesthetics enhance inhibitor neurotransmission (via ___ and ____ receptors).
GABA and glycine
What causes hyperpolarization?
outward current of K+,
Cl= influx,
closure of Ca2+ channels
What causes depolarizatin?
net inward current of:
Na+ influx
Ca2+ influx
Reduced K+ efflux through leaky channels
Ionotropic receptor OR metabotropic receptor???
Conformational change sets in motion a biochemical cascade
Metabotropic
Ionotropic receptor OR metabotropic receptor???
Slower synaptic response
Metabotropic
Ionotropic receptor OR metabotropic receptor???
Muscarinic AChR
Metabotropic
Ionotropic receptor OR metabotropic receptor???
5-HT3R
Ionotropic
Ionotropic receptor OR metabotropic receptor???
Conformational change gates a pore
Ionotropic
Ionotropic receptor OR metabotropic receptor???
Nicotinic AChR
Ionotropic
Ionotropic receptor OR metabotropic receptor???
Opioid Receptor
Metabotropic
Ionotropic receptor OR metabotropic receptor???
Fast synaptic response
ionotropic
List 2 gases that are unconventional NT.
NO
CO
What structure connects cells at an electrical synapse?
Gap junctions (connexions form gap junctions)
Which protein in the docking complex is the calcium sensor?
Synaptotagmin
Name 3 signals that open pores in gated ion channels.
Membrane voltage (electrical), chemicals (ligands), and pressure (mechanical)
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
DOPAMINE
Biogenic Amine
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
VASOACTIVE INTESTINAL PEPTIDE (VIP)
Neuropeptide
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
OPIOIDS
Neuropeptide
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
NOREPINEPHRINE
Biogenic Amine
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
ANANDAMIDE
Nonconventional
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
GLUTAMATE
Amino Acid
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
NITRIC OXIDE
Nonconventional
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
GLYCINE
Amino Acid
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
SUBSTANCE P
Neuropeptide
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
GABA
Amino Acid
Sort each NT into the correct pile: Biogenic Amine, Neuropeptide, Amino Acid, or Nonconventional
SEROTONIN
Biogenic Amine
Where are nicotinic acetylcholine receptors NOT located?
a. autonomic ganglia
b. neuromuscular junction
c. chromaffin cells in the adrenal medulla
d. sinoatrial node
D - sinoatrial node
What is the primary NT of peripheral EFFERENT (motor) neural pathways?
Acetylcholine (ACh)
What role does Acetylcholine play in the CNS?
- the modulation of sleep
- wakefulness (in the RAS)
- learning
- memory
Where does Acetylcholine synthesis occur?
In the presynaptic nerve terminal
T/F: Cholinergic receptors can be ionotropic or metabotropic.
True
Are nicotinic ACh receptors ionotropic or metabotropic?
ionotropic
Are muscarinic ACh receptors ionotropic or metabotropic?
metabotropic
Cholinergic describes neurons or synapses that use ____ as the neurotransmitter.
Acetylcholine
Acetylcholine is the primary NT of peripheral efferent or afferent neural pathways?
EFFERENT
List all the places ACh is a NT at:
1.
2.
3.
4.
5.
- NMJ
- Autonomic ganglia
- Terminal synapses of parasympathetic postganglionic fibers
- Few sympathetic postganglionic fibers (sweat glands)
- NOn-neuronal cholinergic system (NNCS)
T/F: Only nicotinic receptors are expressed in the central neurons, not muscarinic receptors.
False - both are
What are the substrates of acetylcholine?
choline and acetyl-CoA
What is the rate-limiting factor for the availability of Acetylcholine?
The availability of its substrates (choline and acetyl-CoA)
How does glucose enter nerve terminals?
by passive transport (facilitated diffusion)
Glycolysis converts glucose to ______.
pyruvate
Where does glycolysis occur?
in the cytoplasm
An acetyl group from pyruvate is added to coenzyme A to produce _____.
acetyl-CoA
Choline is ______ transported into the presynaptic terminal.
actively
________ is the rate-limiting step in ACh synthesis.
Choline transport
What catalyzes the formation of ACh from acetyl-CoA + choline?
Choline acetyltransferase (ChAT)
Where is ACh stored?
In synaptic vesicles until release
How is ACh transported into vesciles?
By an H+-antiporter (exchanger)
_____ triggers vesicle fusion at the active zone, and ____ is released into the synaptic cleft by exocytosis.
Increased intracellular Ca2+; ACh
What hydrolyzes ACh? What is it hydorlyzed to?
Acetylcholinesterase (AChE); acetate + choline
What happens to the choline that is produced durign ACh hydrolysis?
It re-enters the nerve terminal and is reused for ACh synthesis
What is an antagonist of Ca2+ at the presynaptic nerve terminal?
Mg2+
Why does Mg2+ cause muscle weakness or potentiate NM block?
It is an antagonist of Ca2+ at the presynaptic nerve terminal
Nicotinic ACh recetpors (nAChR) are inotropic or metabotropic receptors?
Inotropic
T/F: nAChRs are nonselective anion channels.
F - nAChRs are nonselective cation channels.
Describe the structure of nAChRs.
They are pentameric complexes with 2 agonist binding sites - one at the extracellular 𝜶/ε interface of one 𝜶 subunit and the 𝜶/𝛅 interface of the other 𝜶 subunit
What is required to initiate the conformational change that opens the nAChR channels?
simultaneous binding of 2 ACh molecules to the alpha subunits
Where are NmAChRs found?
in skeletal muscle at the NMJ
Where are NnAChRs found?
in the autonomic ganglia, on the chromaffin cells of the adrenal medulla, and in the CNS
As their name implies, nAChR can be opened by the ____plant, _____.
tobacco plant, alkaloid nicotine
Muscarinic ACh receptors (mAChR) are inotropic or metabotropic receptors?
Metabotropic
Where are muscarinic AChRs found?
CNS, heart, smooth muscle, and glands of GI tract
_____ mediate most action of ACh in the CNS.
mAChR
Muscarinic AChRs are so named b/c they are activated by ____, a _____ found in a poisonous mushroom.
muscarine, a toxic alkaloid
How many types of mAChR have been identified?
5
Where are NM (nicotinic ACh) receptors found?
Skeletal muscle at NMJ
What is the signal transduction of NM (nicotinic ACh) receptors?
Opening of nonselective cation channels –> influx of Na
