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47 Cards in this Set

  • Front
  • Back
2 major types of receptors
ionotropic and metabotropic
Define ionotropic receptors
ligand gated ion channels
Define metabotropic receptors
ligand-induced second messenger generators that alter the "metabolism" of the cell
which receptor has fast onset and termination
Which receptor shows amplification of response and diversity
are there transmitters that bind to both iono and metabotropic receptors
yes, Ach, GABA, Glutamate
Describe location of ionotropic and metabotropic receptors
ionotropic are often located near transmitter release sites, metabotropic are usually not near transmitter release sites
Name Ach ionotropic receptor
Name Ach metabotropic receptor
name model organism for study of nicotinic Ach receptors
electric organ of Torpedo electric fish
How many subunits are there in nAchR
5 subunits - 2 alpha, beta, gamma and delta, all 5 subunits form staves on barrel arrangement
Describe subunit of nAchR
4 regions (M1-M4), M2 from each subunit forming lining of pore
Which subunit has binding sites for transmitter
alpha subunits
What happens when Ach binds to receptor
if only one Ach binds will have brief flickering, if 2 Ach bind will have normal opening
Name toxins that block Ach binding
alpha bungarotoxin/curare
describe ion selectivity of Ach receptors
multi ion selectivity - equally permeable to Na and K. some permeability to Ca, depends on alpha subunit 7
what is the equilibrium potential of Ach receptor
0 mV
Name 2 classes of glutamate receptors
NMDA and non NMDA
What NMDA stands for
N mmethyl D aspartate
Describe NMDA receptor
-activated by NMDA agonist
- high conductance (50 pS)
-permeable to Ca, Na, K
-pore is plugged by Mg at resting potential, plug is removed by depolarization
-relatively slow gating
-lots of modulatory sites (glycine, Zn, PCP)
Name 2 classes of non NMDA receptors
AMPA and kainate
Describe non NMDA receptor
-lower conductance (20 pS)
-permeable mostly to only Na and K
-fast gating
what is the most common inhiitory NT
GABA, inhibitory because does not conduct Na or K , but Cl, used by many interneurons
Ionotropic GABA receptor is..
ligand gated Cl channel
Chloride is _ outside, _ inside
high, low
Equilibrium potential for Cl channel
Pertussis toxin
travels across cell membrane and inactivates galpha i protein and g alpha 0 , uncouples and prevents action of metabotropic receptor
what happens if add NT and receptor is metabotropic
will inhibit activity
what effects which pathway you chose
primary effector effects, not g protein or receptor
Direct pathway
g protein directly associates with final receptor
what is most common direct pathway
beta gamma
How do you know beta gamma acts on K channel directly
use reconstitution, overexpress K channels
How many subunits does g protein have
3 subunits - alpha beta gamma
describe g protein in resting state
all three subunits associate with each other and receptor, alpha subunit binds GDP (high affinity)
what happens to g protein when NT binds
it loses affinity for GDP, and binds GTP since its more abundant, alpha dissociates from beta and gamma
How does alpha subunit inactivate
it turns itself off since it is a slow GTPase, when GTP is cleaved back to GDP, complex reassociates and protein returns to active state
what experiments can be done to prove GTP is used
1) remove GTP
2)replace GTP with GTP gamma s which is non hydrolyzable form and will cause persistent activation
3)replace with GDP beta s which has high affinity binding to alpha subunit of g protein will causes block of signaling
what determines diversity and specificity of actions
1. specific g protein receptor interactions
2.use of either beta gamma or alpha subunits
3 diverse second messenger cascades
Specific g protein receptor interactions
there are 20 alpha, 5 beta 7 gamma subunits, allows number of combinations
Describe antisense oligonucleotides experiment
inject into cells sequence of about 20-30 amino acids that is complimentary to MRNA that codes for g protein. When bound, mRNA will be double stranded and will not be translated into protein, after time protein will be depleted
Both somatostatin and Ach reduce Ca, is it same g protein
no, uses different alpha, beta and gamma subunits, this may reduce crosstalk , allows for specificity
Receptor signaling compartmentalization
receptor , g proteins and interacting proteins are all within different compartments of the cell
General scheme of messenger action
First messenger-->receptor-->transducer-->primary effector-->second messenger--> secondary effector
what does activation of muscarinic receptors do in heart cells
opens K+ channels causing hyperpolarization and decreasing heart rate
How do you do reconstitution
inject oocyte with GIRK channels and g protein subunits
what happens when you express beta gamma RNA with GIRK channel but exclude GTP
doesnt block beta gamma effect
same but add GDP beta s
doesnt block beta gamma effect