Ligand-Gated Ion Channels and G-Protein Coupled Receptors Flashcards
1
Q
The largest group of transmembrane signaling proteins is __________.
A
GPCRs
2
Q
True or False: when receptors are not bound to anything they aren’t doing anything. Why or why not?
A
False.
They are in a dynamic state, constantly shifting conformation.
3
Q
Receptors are usually embedded in the ________ but can also be found in the _______.
A
cell membrane
cytoplasm
4
Q
What is a ligand and what is its function?
A
a chemical messenger: a small molecule or peptide
binds to receptors and stabilizes a conformation of the receptor
5
Q
What does a conformational change do the the receptor?
A
changes its shape which induces downstream signal transduction
6
Q
Drugs can only _______ or _______ the body’s own regulatory molecules, not give a cell ________.
A
mimic or block
new function
7
Q
Receptors are ________ for physiologic processes.
A
normal points of control
8
Q
Receptor function is regulated by _______ supplied by the _______.
A
molecules
body
9
Q
An agonist is a drug that combines with a receptor to__________ a target organ.
A
stimulate
10
Q
An antagonist is a drug that combines with a receptor to ________ with a naturally occurring _______ or ______.
A
interfere
agonist or agonist drug
11
Q
_________ is how drugs interact with receptors and produce varying effects.
A
Therapeutic response
12
Q
Affinity/Potency is ________. Therefore, low potency necessitates _______.
A
how tight the drug-receptor bond is.
more drug
13
Q
Intrinsic activity/efficacy is ________.
A
intrinsic response when drug administered that gives maximum activity
14
Q
A ligand that binds to a receptor and activates it is called an _______.
A
agonist
15
Q
A ligand that binds to a receptor and prevents it from inactivating is called an ________.
A
antagonist
16
Q
An agonist works by _________.
A
stabilizing an active conformation of the receptor
17
Q
An antagonist is designed to ________ of an agonist. Therefore, if there is no endogenous agonist, the antagonist will _________. There has to be something to _______.
A
get in the way
not have an effect
antagonize
18
Q
An orthosteric antagonist is ________. Also called _______.
A
a ligand that blocks signaling by competing with the endogenous agonist for the main binding site of the receptor
competitive antagonist
19
Q
An allosteric antagonist is ________. Also called ________.
A
a ligand that binds to an accessory binding site (not the main site for activation) in order to hinder the activity of an agonist
non-competitive antagonist
20
Q
A pore blocker is a type of ________ that ________.
A
antagonist
physically obstructs the channel
21
Q
A receptor can fluctuate between natural conformations. Some are associated with _______, while others are not.
A
pharmacological activity
22
Q
Drugs can activate or inactivate receptors by _______ a pharmacologically significant __________ by binding to _________ or _________ site.
A
stabilizing
conformation
orthosteric
allosteric
23
Q
Antagonists can be either ________ or ________.
A
competitive or non-competitive
24
Q
A partial agonist weakly stabilizes _______ or stabilizes _________ which produces a ________ response than a full agonist.
A
active site
partially active state
lower
25
Inverse agonists stabilize ________ which reverses baseline receptor activity. Differ from an antagonist in that they produce an effect whether or not there is an ________ present.
inactive state
| agonist
26
A noncompetitive agonist will ________ the _______ response of an agonist. On a Dose-Response curve the height of the curve will be ________, therefore affecting the drug's _______ on the ______-axis.
```
decrease
maximal
lower
efficacy
y
```
27
A competitive agonist will _______ amount of agonist necessary to produce a given intensity of response. Therefore the graph will shift _______, therefore affecting the drug's ________ NOT its ______ efficacy.
increase
right
dose required
maximum
28
What are four types of receptors that represent 99% what our drugs work on?
ligand-gated ion channels
GPCRs
kinase-linked receptors (KLR)
nuclear receptors
29
Kinase-linked receptors (KLR) function by ________. They are one of the _______ types of receptors, it takes _______ because it is changing what _______ are being expressed.
once activated (extracellular domain), enzyme cascade on inside of cell stimulates gene trascription
slower
hours
genes
30
Nuclear receptors are located in the _______ and typically respond to ____/____. A ________ molecule or ligand binds with receptor which stimulates ________. This process takes ______.
```
cytoplasm
steroids/thyroid hormones
lipid-soluble
gene transcription
hours
```
31
The fastest type of receptor is ________. They work in ________. They work by moving ions _______ to produce cellular effects.
ligand-gated ion channels (ionoctropic receptors)
milliseconds
against their electrochemical gradient
32
When an ionotropic receptor is opened it can result in ________ or _______ depending of the _______ of the ion and the ________ of their movement.
depolarization
hyper-polarization
charge
direction
33
A GPCR or _______, act slowly, on a ______ timescale because the process requires a __________ and ________. GPCR initiates chain reaction that results in ________ which triggers a _________.
```
metabotropic receptor
second
second messenger and several steps
enzyme cascade
cellular response
```
34
Examples of ionotropic receptors:
nicotinic Ach receptor
serotonin receptor
ATP receptor
35
Examples of GPCR:
glutamate receptors
adrenergic receptors (alpha & beta)
GABA receptor
muscarinic Ach receptor
36
A kinase is an enzyme that does ________ which activates an _________.
phosphorylation
| enzyme cascade
37
Example of nuclear receptors:
steroid receptors
38
Examples of receptor kinases:
insulin, growth factors, cytokine receptors
39
Structure for ligand-gated ion channels:
oligomeric (4-5 subunits) subunits surrounding central pore
40
Structure for GPCRs: _______. Many GPCRs exist as ______.
monomeric or oligomeric
7 transmembrane helices (alpha, beta, gamma subunits) w/ intracellular G-protein coupling domain, 3 extracellular loops, 3 intracellular loops
dimers
41
Structure for receptor kinases:
single alpha helix links extracellular receptor and intracellular kinase domain
42
Structure of nuclear receptors:
monumeric, w/ DNA binding and receptor binding domains
43
A GPCR is located in the __________. Effector is via a _______ or _______. It couples via ______ or ______.
cell membrane
channel or enzyme
G-protein or arrestin (ARR)
44
A ligand-gated ion channel is located in the _______.
| Its effector is an ________. Its coupling is _______.
cell membrane
ion channel
direct
45
Receptor kinases are located in the _______. The effector is ________. Coupling is ______.
cell membrane
a protein kinase
direct
46
Nuclear receptors are located in the _________. Its effector is ________. Coupling occurs via _______.
intracellularly
gene transcription
DNA
47
Cells communicate with one another via _______.
action potentials
48
Resting cell membrane potential is overall ______ at a charge of ________.
negative
| -70 mV.
49
Excitatory means cell's charge is approaching _____, either by letting _______ into cell or letting _______ out of cell- making the cell more _________.
0 mV
positive ions
negative ions
positive
50
Excitatory means cell's charge is approaching _____, either by letting _______ into cell (_______ ) - making the cell more _________.
0 mV
positive ions
Na+, Ca 2+, K+
positive
51
Inhibitory means cell's charge is approaching _____, either by letting _______ into cell (_____) or letting _______ out of cell.
negative
negative ions
Cl-
positive ions
52
When the cell is in an excitatory state, it becomes ______, which opens ________ allowing _______ ions to move _______ cell via their ________.
```
depolarized
ion channels
positive
into
electrochemical gradient
```
53
When the cell is in an inhibitory state, it becomes ______, which opens ________ allowing _______ ions to move _________ (or ______ ions out) cell via their ________.
```
hyperpolarized
ion channels
negative
into
positive
electrochemical gradient
```
54
Voltage-gated ion channels respond to a difference in __________.
transmembrane potential
55
Nicotinc Ach/Cys-loop receptors, GABAa receptors, glycine receptors are examples of _________ ligand-gated ion channels.
pentamer
56
NMDA receptors, glutamate receptors, AMPA receptors, Kainate receptors are examples of _______ ligand-gated channels.
tetramer
57
_______ is an example of an NMDA (N-methyl-D-aspartate) receptor.
ketamine
58
Ligand-gated channels are made of ________ surrounded by a central ________ which influence which ions are let through. Agonist binding ______ pore.
several subunits
ion pore
opens
59
CYS-Loop receptors are named because of the loop formed by ________ between 2 _______ near N-terminus.
disulfide bonds
| cysteines
60
CYS-Loop receptors are made of ____ subunits around central pore.
5
61
5 types of subunits are: _______. Receptors are made of different combinations of these types of subunits.
alpha, beta, gamma, delta, and epsilon.
62
Examples of excitatory receptors are _______ and ______. Examples of inhibitory receptors are _______ and ________.
nicotinic Ach and serotonin
| glycine and GABAa
63
GABAa receptors control almost all of the _______ signaling in the ________.
inhibitory
| CNS
64
Cation receptors are lined with ________ while anions are lined with _______ to help with the passage of ions through the pore.
negative ions
| positive ions
65
Gating refers to _______.
the opening (activation) or closing (by deactivation or inactivation) of ion channels
66
In agonism, ________ needed to bind to _______ of receptor which causes a conformational change in receptor allowing the pore to open and let ions in.
x2 ACh
| 2 alpha units
67
________ are responsible for obstructing ion pore in a receptor.
Alpha sub units
68
Two types of Cys-loop receptors are:
nicotinic acetylcholine receptors and GABAa
69
3 types of glutamate receptors are:
NMDA receptors
AMPA receptors
Kainate
70
Two examples of chemicals that work on Nicotinic Ach receptors:
nicotine, Varenicline (Chantix)
71
Four examples of chemicals that work on GABAa receptors:
Ambien (zolpidem), barbituates, benzodiazepines, alcohol
72
Aniracetam (cognition-enhancer) is an example of an _________.
AMPA receptor
73
Nicotinic ACh receptors are located at the _______ and in the ______.
NMJ
| CNS
74
Nicotinic ACh receptors in the NMJ and CNS are structurally _________, which allows drugs to be designed so that _______. In the NMJ, ACh receptors contain _________ subunits while neuronal ACh receptors only contain _________ subunits. There are a total of ______ subunits.
```
slightly different
they affect one receptor type without affecting the other
alpha, beta, delta, gamma
alpha and beta
5
```
75
In the brain, NAChRs _________, increasing the number of receptors in response to chronic _________, like in ________.
up-regulate
nicotine
smoking
76
NACHRs can either be in one of 3 states:
desensitized, closed or open
77
A desensitized receptor _______ responsiveness when it is _________ exposed to ________.
decreases
repeatedly
agonist
78
AMPA and Kainate receptors are a type of _________ receptor, are _________, and allows ________ ions to pass.
ionotropic glutamate
excitatory
Na+, K+
79
NMDA receptors are a type of ________ receptor, are _______, and allows ________ ions to pass.
ionotropic glutamate
excitatory
Na+, K+, Ca 2+
80
Ionotropic glutamate receptors are composed of _____ subunits and have a ______ structure. Each subunit has ________, the second one forms the ______.
4
loop
4 transmembrane domains
ion pore
81
The NMDA receptor requires its _____ binding sites to be occupied in order to open. ________ for ______ and ______ for ______ (although it is usually ______).
4
2 for glutamate
2 for glycine
inhibitory
82
Glutamate receptors experience _________, which occurs when a synapse experiences ______ activity which creates a ________ response because of the _________ of receptors due to this activity.
Long Term Potentiation
increased
stronger
up-regulation
83
Long Term Potentiation is implicated in ________, which is the brain's ability to _______ and ______ based on stimuli.
neural plasticity
adapt
change
84
At resting membrane potential in NMDA receptors, the pore is blocked by ________. _________ causes it to move because it is _______- dependent.
Mg 2+
depolarization
voltage
85
NMDA receptors are special because they allow ______ to pass, activating _______ which controls neural excitability by regulating _______ release. This leads to ________ being inserted into the synapse.
Ca 2+ ions
CaMKII (camkinase II)
vesicle
AMPA receptors
86
AMPA receptors result in a ________ synapse because
| of their role in the _______ of excitatory transmission in the CNS and plays an important role in _______.
stronger
majority
neural plasticity
87
Coincidence detectors influence neuronal information processing by reducing ________, reducing _________, and forming associations between separate _________.
temporal jitter
spontaneous activity
neural events
88
________ of our genome is dedicated to _______ coding.
3%
| GPCR
89
More than half of current pharmaceuticals target _________.
GPCRs
90
There are ______ main classes of GPCR: ____, ____, and ____.
3
| Class A, B, and C
91
Examples of Class A GPCR receptors are (2):
adrenergic receptors, muscarinic ACh receptors
92
Examples of Class B GPCR receptors are:
parathyroid hormone receptor
93
Examples of Class C GPCR receptors are (2):
metabotropic glutamate receptors, GABAb receptors
94
GABAa receptors function by: ________. While GABAb receptors function by: ________.
GABAa: postsynaptic fast inhibition, inhibition via Cl- into cell
GABAb: postsynaptic slow inhibition, pre-synaptic Ca 2+ reduction, postsynaptic inhibition via K+ ion out of cell
95
G alpha s subunits activate ________ and increase _________. This has ______ effects depending on the _______ it is in. For example, in the SA node it increases ______, and _______ the smooth muscle.
```
adenylyl cyclase
cAMP
tissue
HR
relaxes
```
96
G alpha i subunits _______ adenylyl cyclase and ________ cAMP, it causes _______.
inhibit
decreases
vasoconstriction
97
Adenylyl cyclase (AC) helps to convert ________ to _______.
ATP to cAMP
98
cAMP is a ________. Which is an _______ signaling molecule, bringing in molecules and their effects to the cell because they are unable to cross _________.
second messenger
intracellular
cell membrane
99
A first messenger is found _______ and stimulates _______ activity.
extracellular
| intracellular
100
G alpha q subunits activate _________ which hydrolyzes _________, causing an increase in _____ and _______ and ultimately a release of _______ from intracellular stores. This results in _______.
```
phospholipase C (PLC)
phosphoinositol
IP3
DAG
Ca 2+
contraction
```
101
IP3 and DAG are examples of __________.
second messengers
102
A second messenger activates _________ pathways that amplify the signal and culminate with the _________ of transcription factors, inducing a ________.
intracellular signaling
activation or inhibition
cellular response
103
Increased levels of cAMP stimulates an increase in ________, which is responsible for the transfer of ________ from ______ to _______.
protein kinase A (PKA)
phosphates
ATP
other molecules
104
Receptors activate g proteins which target _______, which stimulate _________, which increase _______ that stimulate ________.
enzymes
second messengers
protein kinases
effectors
105
Examples of GPCR downstream targets are (5):
enzymes, transport proteins, contractile proteins, hormones, and ion channels
106
The _______ of a G protein-coupled receptor (GPCR) response can be described as the loss of _______ subsequent to _________ administration of an _______.
desensitization
response
prolonged
agonist
107
Desensitization is a _______ mechanism to prevent __________ of a receptor. This is accomplished by the binding of ________ to the receptor, which tags it for _________. This causes a ______ in drug response and contributes to drug ________.
```
protective
overstimulation
Beta-arrestin (ARR)
internalization
decrease
tolerance
```
108
Once internalized, the GPCR-beta-ARR complex can act as ________ inside of cell. beta-ARR signaling illicits a __________ effect than normal. Decrease in GPCRs causes a ___________ in drug effect.
protein scaffold
different
decrease
