Lec 17 Flashcards
What is defined as “ a process that is generally slow and often involves a receptor molecule that is different than the ion channel that is affected.”
Modulation (a metabotropic or Gprotein coupled action)
What type of receptor is present when the primary receptor is a physically separate molecule that communicates to the channel molecule through 2nd messengers?
metabotropic receptor or Gprotein receptor
Widely divergent networks of neural pathways (one neuron branches to many neurons) are examples of what type of system?
modulatory systems
more general alterations of the brain are controlled by what type of systems? (eg. falling asleep, waking up, attentive)
modulatory systems
Modulatory systems generally use what type of chemical synapse?
metabotropic synapse or receptors
what is it called when an input changes the responsiveness of a cell according to other inputs?
modulation
What is the metabotropic receptor for ACh?
muscarinic receptor
What is the metabotropic receptor for Glutamate?
mGluR
What is the metabotropic receptor for GABA?
GABAb
What is the metabotropic receptor for Glycine?
there isn’t one.
What is the metabotropic receptor for catecholamines?
a1,a2,B,D1,D2
metabotropic receptors for catecholamines are primarily found in what nervous system?
ANS
What is the metabotropic receptor for Anandamide?
Cannabinoid R –> natural ligand in weed can activate
What is the ionotropic receptor for the ligand ACh?
Nicotinic receptor
What is the ionotropic receptor for the ligand Glycine?
NMDA, AMPA (GluR?)
What is the ionotropic receptor for the ligand GABA?
GABAa
What is the ionotropic receptor for catecholamines?
there isn’t one
What is the ionotropic receptor for Anandamide?
there isn’t one
What studied ligands do not have a metabotropic receptor?
Catecholamines and Anandamide
GPCRs generally have how many TM regions?
7 TMs
A classical second messenger cascade:
what happens following the binding of an agonst to the GPCR?
the activated receptor interacts with the aBy heterotrimer to promote a conformational change that facilitates the release of bound GDP and simultaneously binds GTP to alpha subunit.
A classical second messenger cascade:
What happens following the binding of GTP to the a subunit of the Gprotein?
the GDP-GTP exchange stimulates dissociation of the Gprotein complex from the receptor.
A classical second messenger cascade:
What happens follow the dissociation of the Gprotein from its receptor?
disassembly of the trimer into a free alpha subunit and “By” (beta-gamma) subunit
A classical second messenger cascade:
What happens after the disassembly of the trimer?
- The free active GTP-bound alpha subunit can now interact in the plane of the membrane with downstream effectors such as adenylyl cyclase and phospholipases
- and the “By” subunit can now activate ion channels or other effectors
A classical second messenger cascade
What happens after the GTP-bound alpha subunit, and By-subunit bind to downstream effectors or ion channels?
Termination:
alpha subunit terminates the signalling events that are mediated by the alpha and “By” subunits by hydrolyzing GTP to GDP and inorganic phosphate.
alpha complex becomes inactive –
a-GDP complex then rejoins with “By”-subunits and dampens signal transmission
Which of the Gprotein subunits is a GTPase?
alpha subunit
Which Gprotein subunit terminates the function of 2nd messenger complexes?
alpha subunit terminates itself (dephosphorylates itself)
Simple signal amplification though GPCRs:
list the 6 steps following the release of a NT:
- NT activates the receptor
- Receptor activates Gprotein
- Gprotein stimulates effector (adenylyl cyclase to convert ATP to cAMP)
- cAMP activate protein kinase A
- Protein kinase A phosphorylates potassium channels
GPCR or metabotropic receptors have 2 general different functions:
- activate distant channel protein with second messengers
2. direct modulation via “By”-subunit (moving in the plane of the membrane)
a GIRK channel can be innervated by a ________
muscarinic ACh metabotropic receptor . GPCR
Muscarinic activation of Gproteins in the heart muscle lead to…
opening of K+ channels through a direct effect of by By-subunit.
In cardiac muscle, what receptor is used to open K+ channels by a By-subunit?
Muscarinic AChR
What protein is needed to reduce the amount of cAMP being produced?
(Gi) inhibitory Gprotein alpha subunit.
By activating an inhibitory Gprotein , What will the nearby adenylyl cyclase be affected?
it will inhibit the conversion of ATP to cAMP
the second messenger cAMP activates what kinase?
protein kinase A
phospholipase C splits PIP2 into what 2 second messengers?
IP3 and DAG
IP3 and DAG are second messengers that originate from the activation of what effector protein?
Phospholipase C
the release of IP3 into the intracellular membrane causes what effect?
release of Ca2+ from the ER
release of DAG into the intracellular membrane causes what effect?
activation of protein kinase C
one GPCR can activate how many Gproteins?
many
what is an example of a divergent NT?
norepinephrine
Define Divergent Neurotransmitter?
a single NT that can bind the multiple receptors and affect multiple GPCR and create multiple different responses.
(one NT and multiple channels and effects)
Define Convergent Neurotransmitter?
when multiple NT bind to their own specific receptor , via the same or different second messenger, and influence the same set of channels.
(multiple NT and 1 channel and its effect)
A “By”subunit of a Gprotein can activate what effectors?
open GIRKs Phospholipase C GPCR kinases Adenylyl cyclase PI-3 kinase several protein tyrosine kinases (MAPK)
A “By”subunit of a Gprotein can inhibit what effectors?
N-type Ca channels
possibly adenylyl cyclases
How will a “By”subunit of a Gprotein affect a GIRK channel?
it will close the GIRK
How will a “By”subunit of a Gprotein affect a GPCR kinase ?
it will activate it
How will a “By”subunit of a Gprotein affect a phospholipase C ?
it will activate it.
How will a “By”subunit of a Gprotein affect adenylyl cyclase ?
it will be activated or inhibited
How will a “By”subunit of a Gprotein affect PI-3 kinases ?
it will be activated
How will a “By”subunit of a Gprotein affect MAPK or protein tyrosine kinases ?
they will be activated
How will a “By”subunit of a Gprotein affect N-type Ca channels?
they will be inhibited
Presynaptic inhibition and Presynaptic facilitation are examples of actions in what type of regulation network?
spatially focussed network
Presynaptic inhibition acts on the presynaptic terminal of the regulation site and inhibits the synapse by…
releasing a NT that will cause a reduction in Ca current in the target presynaptic cell. Little to no NT will be released. Postsynaptic cell potential is decreased.
Presynaptic facilitation acts on the presynaptic terminal of the regulation site and activates the synapse by…
releasing a NT that will cause a reduction in K+ current in the target presynaptic cell. Less K+ ions will slow repolarization and prolong the action potential in the cell and thus increasing the Ca+ influx. Post synaptic cell potential is increased!
By releasing a NT that will cause a reduction in Ca current in the target presynaptic cell. Little to no NT will be released. Postsynaptic cell potential is decreased. What is this an example of?
Presynaptic inhibition
By releasing a NT that will cause a reduction in K+ current in the target presynaptic cell. Less K+ ions will slow repolarization and prolong the action potential in the cell and thus increasing the Ca+ influx. Post synaptic cell potential is increased! this is an example of?
Presynaptic Facilitation
Presynaptic inhibition and Presynaptic Facilitation are examples of what type of modulation?
spatial modulation.
The ascending reticular activating system includes what 2 NT?
serotonin, and norepinephrine
what 2 NT are involved in regulation of wakefulness and arousal?
serotonin, and norepinephrine
What “system” is responsible for the regulating of wakefulness and arousal?
ascending reticular activating system.
Neurons that contain NE and innervate nearly every part of the CNS are located where?
locus coeruleus
The locus coeruleus contains what NT that is responsible for modulation of the CNS?
norepinephrine
What “system” appears to be in the control of mood and emotional behaviour?
serotonin system
Neurons containing serotonin are located in 2 groups called?
raphe nuclei
The raphe nuclei project to most of the brain, what NT is present ?
serotonin
How many primary structures contain serotonin in the brain?
2 (raphe nuclei)
Neurons containing dopamine are located where?
substantia nigra and the ventral tegmental area
where does the substantia nigra project to in the brain?
the straitum
What NT fills the substantia nigra and the tegmental area?
dopamine
what NT is projected through the straiitum?
dopamine
what area projects to the prefrontal cortex and parts of the limbic system?
ventral tegmental area (midbrain)
Where does the dopamine system originate?
substantia nigra
What “system” of modulation is involved in the initiation of voluntary movement ?
the dopamine system
What “system” degenerates and is responsible for Parkinson’s disease?
the dopamine system
What are of the brain is responsible for Parkinson’s disease?
sustantia nigra degeneration
What part of the brain is responsible for reward systems and drug addiction?
ventral tegmental area
Where is the system located that is involved with Hallucinogenic Drugs and antidepressants?
raphe nuclei and project to most of the brain
LSD is an example of what type of drug?
hallucinogen drug
Prozac is an example of what type of drug?
anti depressant
The drug that initiates voluntary movement is located where in the brain?
substantia nigra
Where are the neurons in the brain that contain ACh ?
basal forebrain complex and the pontomesecephalotegmental cholinergic complex
What 2 regions make up the basal forebrain complex?
septal nuclei, nucleus basalis
The neurons in the basal forebrain project where?
to the hippocampus and the neocortex
Where does the pontomesecephalotegmental cholinergic complex projects to the..
dorsal thalamus and part of the forebrain
What NT is located in the pontomesecephalotegmental cholinergic complex?
ACh
what are the 4 modulatory systems in the CNS brainstem?
ACh System, dopamine system, serotonin system, ascending reticular activating system.
What occurs when a transmitter or hormone influences the responsiveness of a channel or a cell to other stimuli?
Modulation
NE has what affect on the AHP in decreasing spike frequency adaptation?
NE decreases AHP by inhibiting a Ca dependent K+ channel and thereby decreasing spike frequency adaptation.
What NT modulates AHP by inhibiting Ca dependent K+ channel and thereby decreasing spike frequency adaptation?
Norepinephrine
What NT modulates and decreases spike frequency adaptation?
Norepinephrine
What is the result of NE decreasing AHP and inhibiting Ca dependent K+ channels ?
decreasing Spike frequency adaptation
a neuron from the hippocampus “by control” undergoes sustained depolarization from injected current, What kind of action potential response takes place?
Phasic – spikes and adapts to no APs
a neuron from the hippocampus “by adding NE” undergoes sustained depolarization from injected current, What kind of action potential response takes place?
Tonic – causes the spiking from the depolarization stage to be sustained longer.
Phasic action potential response means…
spikes and adapts by eventually having no APs
Tonic action potential response means..
causes constant spiking from depolarization stage by sustaining it longer.
What type of receptor stimulation enhances Ca2+ current through a cAMP-dependent mechanism?
B-Adrenergic stimulation (isoproterenol)
By injecting isoproterenol what happens to Ca and Ba current?
it is increased 2x! (more negative)
what type of stimulation is caused by isoproterenol?
B-adrenergic stimulation
