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