Week 4 Flashcards
(54 cards)
1
Q
Chemical Sensitive/Ligand sensitive channels
A
Ligand binds–>conformational change–>opens gate
2
Q
2 common features of ligand sensitive channels
A
- all membrane spanning proteins and region of synapse binds to NT
- Mediate and effector function of conformational change
3
Q
Ionophoric channels
A
Receptors that gate ion channels DIRECTLY (receptor and gate one piece)
- Recognition site & channel are ONE UNIT
- FAST synaptic action
- made of multiple independent subunits
4
Q
Metabophoric channels
A
receptors that gate ion channels INDIRECTLY
- must use 2nd messenger system
- SLOW synaptic action
- made of long amino acid sequence
5
Q
Differences b/w ionophoric or metabophoric channels
A
- Receptors that gate ion channels DIRECTLY on recognition site and channel are ONE UNIT
- receptors that gate ion channels INDIRECTLY have components separate & must use 2nd messenger system - different overall functions (fast vs slow)
- structurallly different
6
Q
Direct/ionophoric channels locations/NT used
A
found in nerve muscle synapses that use ACh
& in CNS-uses Glutamate, GABA, ACh, set of serotonin receptors
7
Q
Indirect/metabophoric channels locations/NT used
A
Found in CNS synapses that use-NE, DA, & serotonin
8
Q
Direct types of channels
A
- ACh
- GABA
- Glutamate
9
Q
ACh receptors
A
- ACh-nicotinic receptor: binds nicotine
2. ACh-muscarine receptor: binds muscarine
10
Q
ACh-nicotinic receptor (subunits & process)
A
in nerve muscle synapse
- 5 subunits: 2 alpha, Beta, Gamma, Delta
- ->ACh binds to each alpha unit
- ->Na+ influx & K+ efflux
- ->EPSP
11
Q
ACh receptor subunits
A
each has 4 alpha-helical structures (M1-M4)
- M2 lines lumen
- ->3 rings of negative charge, rotate and change conformation
-wide mouth on external side, narrows for selection, opens to inside
12
Q
ACh receptor response
A
causes EPSP
-lumen has to be larger than passive channels to flux BOTH Na+ and K+
13
Q
GABA receptors (subunits & process)
A
2 alpha, 2 beta, gamma
- GABA binds to alpha subunits
- ->allows for Cl- influx (IPSP)
- alpha subunit has highest affinity for GABA
- M2 results in selection for anions
14
Q
Benzodiazapenes and GABA receptor
A
Gamma subunit binds benzos
-presence of one ligand increases efficiency/affinity for GABA
15
Q
Barbituates and GABA receptor
A
binds to alpha and beta subunits
-presence of one ligand increases efficiency/affnity for GABA
16
Q
ACh and GABA receptor similarities
A
- genes that encode them are from the same family (subunits very similar)
- each subunits has 4 membrane spanning helical structures (M1-M4)
- M2 member of each subunit in channel lumen
17
Q
ACh & GABA receptor differences
A
GABA receptors-anion selective (Cl-)
ACh receptors cation selective (Na+/K+)
18
Q
Glutamate receptor types
A
- Kainate receptor (AMPA)
- Quisquilate A receptor (AMPA)
- quisquilate B receptor
- NMDA receptor
19
Q
AMPA receptors
A
- Kainate receptor
2. quisquilate A receptor
20
Q
similarities b/w AMPA receptors
A
- both affected by AMPA
- both NOT affected by NMDA
- both LOW conductance cation channels of Na+/K+
* not Ca++
21
Q
Kainate receptor
A
found on motor neurons
22
Q
Quisquilate A receptor
A
binds glutamate and zinc
*zinc needed to open
23
Q
Quisquilate B
A
G protein type receptor
24
Q
NMDA receptor
A
must bind glutamate to function
- binds glycine
- binds zinc
- binds Mg++
- Binds PCP
25
NMDA receptor 2 exceptional properties
1. High conductance-flux of Na+, K+, Ca++
| 2. Plugged by Mg++-->will not operate until Mg++ removed by depolarization
26
Requirements for NMDA receptors to work
- VM must be sufficiently depolarized to blow out Mg++ plug
| - glycine necessary for glutamate NMDA receptor needed to work at all
27
Neurons with both AMPA and NMDA receptors
normally EPSPs due mostly to AMPA receptor/glutamate interactions
-->may be enough to blow out Mg++
28
Synaptic plasticity of post-synaptic side
- synapse with sustained activity-->more Ca++ in synapse
| - prolonged EPSP-->dendritic sprouting (long term potentiation)
29
excitotoxicity
too much Ca++
1. increase free radicals
2. degrade cell membranes
3. degrade proteins
* Huntingtons, Parkinsons, Alzheimers??
30
Metabophores general process
recognition of NT done on one structure
| -activation of same effector accomplished by enzymatic cascade
31
G-protein systems
slow onset, longer lasting effect
1. cAMP
2. Phospho-inositol
3. arachidonic pathway
32
Common features of G-protein systems
1. same gene family
2. single subunit with 7 membrane spanning regions
3. NT bound to receptor site on 7-spanning regions
then activates g-protein
33
Phase 1 of G-protein systems
after NT bound, 1st effector enzyme activated by producing 2nd messenger
34
Phase 2 of G-protein systems
2nd messengers lead to changes in specific proteins within the neuron
35
subunits of G-proteins
3 subunits: alpha, beta, gamma
-Beta & Gamme bound to membrane
-alpha is able to move (less tightly bound)
& has sight for GDP
36
3 classes of G-protein
Gs: stimulate adenylate cyclase
Gi: inhibits adenylate cyclase
Go: unknown-->stimulates phospholipase C (PLC)
37
G-protein system phase 1
1. agonist (NT) binds to receptor
2. NT/receptor complex creates affinity for G-protein with GDP
3. receptor/NT/G-protein complex causes alpha subunit to exchange GDP for GTP
4. whole complex dissociates
5. alpha subunit has GTP & can now activate 1st effector enzyme
38
G-protein system phase 2
1. 2nd messenger directly binds to target protein
| 2. 2nd messenger directly activates 2nd effector enzyme
39
G-proteins amounts vs receptor amounts
G-proteins outnumber receptors so single NT can charge many alpha subunits
-->amplify reaction of small release of NT
40
1st effector enzyme types
1. cAMP-->adenylate cyclase
2. Inositol-->phospholipase C (PLC)
3. Arachidonic-->phospholipase A
41
reaction to addition of phosphate groups to proteins
1. altar conformation-->change function of enzyme
2. altar cytoskeletal protein-->change shape of structural protein (channel)
3. altar proteins that regulate DNA transcription
42
Duration of changes directly limited by other enzymes that...
1. inactivate 2nd messengers
2. remove phosphate groups added to target proteins
* alway present and active to provide constant counder to 1st and 2nd messenger effects
43
cAMP G-protein system
1. adenylate cyclase activated by alpha subunit
2. converts ATP to cAMP (2nd messenger)
3. 2 cAMP activates cAMP-dependent protein kinase
4. protein kinase adds phosphate groups to a target protein
44
All protein kinases have:
1. catalytic subunit: portion of enzyme that does the work
| 2. regulatory subunit: prevent catalytic part access b covering active sites
45
cAMP dependent protein kinase structure
-needs 2 cAMP to bind to regulatory subunit to release catalytic subunit (separate piece)
46
protein kinase C & Ca++/calmodulin-dependent kinase structure
Regulatory & catalytic subunits part of structure that folds over on itself like a jack knife
47
de-Activating enzymes in cAMP system
1. phospho-protein phosphatase-removes phosphate groups
2. Phosphodiesterase-converts cAMP to AMP (removes stimulus)
3. GTPase-converts GTP to GDP on alpha subunit
4. NT must be removed from receptor
48
phospho-protein phosphatase
removes phosphate groups that were added by enzyme
49
phosphodiesterase
converts cAMP to AMP
50
GTPase
converts GTP to GDP on alpha subunit
- ->removes stimulus for adenylate cyclase
- ->dissociates from adenylate cyclase
- re-associate with beta and gamma subunits
51
Inositol system
similar to cAMP with charged alpha subunit
1. 1st effector enzyme-PLC-->cleaves membrane
2. 2nd messengers:
- DAG-stays in membrane
- IP3-travels through cytoplasm
3. IP3 binds to receptors on ER
4. Release Ca++ from ER stores
5. increased Ca++ binds to calmodulin-->Ca++-calmodulin complex
6. Ca++/calmodulin-dependent kinase activated
7. adds phosphate group to target protein
8. DAG activates protein kinase C (translocated to contact membrane and activate)
52
5 issues with G-protein
1. systems can interact with one another
2. often open OR close ion channels via phosphorylation
3. can sometimes act directly on ion channels (no phosphorylation)
4. can altar properties of transmitter receptors (Desensitization)
5. can regulate gene expression
- can be a variety of G-protein systems in same area
- can open normally closed channels
- can also close channels that are normally open
53
Beta subunit significance
can sometimes have direct effect and second messengers themselves
-fast rxns in addition to phosphorylation
54
Repeated activation of G protein
can activate protein kinase to such a high lvl that will phosphorylate transcriptional proteins in nucleus of neuron
-->production of new proteins
