1
Q
what affects ion channel function
A
protein strucure
2
Q
4 points to remember when dealing with ion channel function
A
transmembrane structure, ion selectivity, gating properties, inactivation properties
3
Q
is channel activity random or planned
A
random
4
Q
what does stochastic means
A
random
5
Q
channels rely in how many environments and what are they
A
2, hydrophobic and philic
6
Q
what part of transmembrane structure is hydrophobic
A
lipid bilayer
7
Q
what part of trasnmembrane structure is hydrophilic
A
cytoplasm and extracellular fluid
8
Q
membrane spanning regions are called what
A
transmembrane domains
9
Q
ion channels have how many transmembrane SU
A
6
10
Q
how many times are transmembrane SU repeated
A
4x
11
Q
of the four 6TM SU, how do NA and K TM su differ
A
na are connected, K are separated
12
Q
repeating 6tm su come together to form what
A
pore
13
Q
describe a pore
A
gap thru which specific ions may pass through
14
Q
ion channels are often selective for what
A
one ion
15
Q
why do we want selective ion channels in a neuron
A
so that there can be a change in membrane potential instead of no net movement
16
Q
ion selectivity largely based on what
A
diameter and interaction with water
17
Q
attracted to ions, water forms what, what do they do
A
hydration shells, increase ionic diameter
18
Q
by themselves, which is larger, K or na
A
K is larger alone
19
Q
with hydration shell, which is larger, na or k
A
Na
20
Q
Na+ channel pore width allows what
A
one Na+ with one H2O to pass at a time
21
Q
K+ channel pore do what
A
remove H2O, allowing one K+ to pass
22
Q
How would INa+ (the line on the graph) be affected if you changed Na+ channel dynamics (size, or binding site) to accommodate K+?
A
current graph would be more flat
23
Q
voltage gated channels senses changes in what in what
A
Vm, states
24
Q
describe closed resting gating properties
A
no Iion, but if Vm passes threshold, channel opens allowing Iion
25
open activated is what
Iion occurs
26
closed inactivated is what
Vm, is above threshold, but channel is blocked so no Iion
27
shifts between gating states are what
stochastic
28
what is the center of the 6TM complex
4th TM Subunit
29
another name for 4th TM SU
S4
30
positively charged AAs on S4 are attracted to what
Negatively charged amino acids in the other helices
Negative ions impacting Vm at rest
31
s4 does what to open channel
corkscrews within the membrane to open the channel
32
what is the corkscrew a result of
charges are trying to reassociat e
33
s4 corkscrew initiates what
conformational change
34
describe the inactivation particle
cytoplasmic loop that binds a site within th spore after the channel opens
35
Probability of inactivation depends on what
binding affinity
36
once Vm is below the threshold, what happens to inactivation particle
exits the pore and channel closes
37
Ion channels have ____ repeating subunits of ____ TM domains.
4, 6
38
Channel selectivity is mostly based on _________________ and ____________________________.
ion diameter, hydration shells
39
Hydration shells [increase / decrease] ion diameter
increase
40
Channel opening/activation largely based on conformational change of ___________.
s4 helix
41
Channel closing/inactivation largely based on binding affinity of _______________________.
inactivation particle
42
how do neurons talk
via APs
43
presynaptic partner sends signals to what
postsynaptic partner
44
where is the only place that neurotransmitters are released
axon terminal
45
APs trigger what release across synapse
chemical release
46
a chemical release across synapse may or may not do what
initiate a response in postsynaptic aprtner
47
once released from synapse, what do neurotransmitters do
diffuse and find receptor on post synaptic membrane
48
axon terminals contain what that hold neurotransmitters
vesicles
49
vesicles in axon terminals hold what
neurotransmitters
50
when AP reaches axon terminal , what happens
voltage gated Ca2+ channels open, Ca2+ rushes in
51
Ca2+ entry into neuron triggers what
vesicle fusion and release of neurotransmitters into synaptic cleft
52
where are neurotransmitters released into
synaptic cleft
53
NTs bind what , triggers what
postsynaptic receptors, post synaptic potential
54
EPSP is what kind of potential
depolarizing
55
IPSP is what kind of potential
hyper polarizing
56
describe first experiment suggesting a chemical basis for communication
Dr. Otto Loewi, 1920s, take fluid from a stimulated heart and adding to unstimulated heart slows heart rate
57
vesicles fuse with what
cell membrane
58
vesicles positioned with what only found at membrane
specific structures
59
where do vesicles come from
originate in ER and Golgi
60
how are vesicles positioned at the membrane , what specifically do they do
active zones, which hold vesicles in position to fuse
61
active zones contain what
various proteins that create a scaffolding system to tether vesicles and Ca2+ channels
62
why is synapses at NMJ different
muscle fibers have different membranes
63
is motor end plate large or small, what does this mean
large, lots of receptors
64
is NT release normally distributed
yes
65
what does NT release being quantal mean
it occurs in multiples of a fundamental unit
66
what are mini PSPs
things that postsynaptic cells will elicit, tiny PSPs that are released sporadically, even without stimulus
67
at the NMJ, what are mini PSPs called
mini end plate potentials
68
if there is no stimulation, describe MPSP release
they are released in the same amplitude
69
if there is stimulation, describe mPSP release
MN evokes mEPPs with amplitudes that were multiples of mPSPs.
70
describe Poisson distribution
events occur at fixed, discrete intervals
71
same amount of NT is packaged in each vesicle called what
1 quanta
72
each quanta can generate what
a unit mEPP
73
number of vesicles released by a single AP
quantal content
74
what letter represents quantal content
m
75
2 things that quantal content depends on
number of vesicles available to be released, probability that a vesicle will fuse presynaptic membrane
76
M = what
n*P
77
n stands for what
number of vesicles available to be released
78
p stands for what
probability that a vesicle will fuse presynaptic membrane
79
Response amplitude evoked by a single vesicle
quantal size
80
quantal size represented by what letter
q
81
3 things that quantal size depends on
amount of neurotransmitter packed into each vesicle, probability that nay given neurotransmitter will be released, number of postsynaptic receptors available to be bound
82
If there are 30 docked vesicles (n=30) and a 10% probability that any given vesicle will fuse upon arrival of an action potential (p=.10), what is the quantal content?
3
83
If there are 3 docked vesicles (n=3) and a 10% probability that any given vesicle will fuse upon arrival of an action potential (p=.10), what is the quantal content?
0.3
84
amplitude decreases with what
successive PSPs
85
why does amplitude decrease with successive PSPs
- Depletion of available vesicles.
- Auto-inhibition (pre-synaptic neuron can release transmitter that inhibits its own activity)
- Desensitization of postsynaptic receptors
86
why would amplitude increase with successive PSPs
residual presynaptic Ca2+
87
how do neurons talk? list 3 steps
1. app reach axon terminal, V gated Ca2+ channel open, Ca2+ rushes in
2. vesicles fuse membrane, release NT into synaptic cleft
3. NT bind post synaptic receptors and trigger a PSP
88
True/False: NT release follows a normal distribution
false
89
Quantal content (m) depends on _______________ and _________________.
number of vesicles, probability of fusion
90
Quantal size depends on ________________________, _____________________, and _________________________.
amount of NT in vesicles, probability of release, # of Postsynaptic receptors available to be bound
91
PSP amplitude can decrease over time (___________) and increase over time (___________).
depression, facilitation
92
number of vesicles released by a single AP is what
quintal content
93
quantal content dictated by what
n and P
94
response amplitude evoked by a single vesicle
quintal size
95
Postsynaptic cells will elicit tiny PSPs sporadically, even without stimulus called what
mini PSPs
96
what are mini PSPs called at NMJ
mEPPs, mini end plate potentials
97
3 types of vesicles pools
readily releasable pool, recycling, reserve
98
docked and primed, which pool
readily releasable pool
99
Post-fusion, being recycled.. which pool
recycling pool
100
Bound to actin; inactive... what pool
reserve pool
101
what is the vesicular life cycle
1 – Go to presynaptic membrane
2 – Dock at active zone
3 – Priming for release
4 – Fusion and NT release
5+6 – Endocytosis and recycling
102
vesicle membranes contains many what
proteins
103
what does vesicle membrane containing many proteins help accomplish
allows various proteins to interact with the membrane and accomplish each step of the vesicles life cycle
104
Rab GTPases do what
guide vesicles to and with in axon terminal
105
guide vesicles to the active zone, between organelles, allow endocytosis, etc.
different Rabs
106
SNAPs stands for what
soluble NSF attachment proteins
107
SNARES stands for what
SNAREs
108
v snares are what
vesicle snares
109
t snares are what
target snares or terminal snares
110
form complexes that hold vesicles at membrane
SNAPs and SNAREs
111
describe docking
synaptobrevin binds SNAP-25 and syntaxin
112
synaptobrevin is what
vSNARE
113
syntaxin is what
tSNARE
114
describe priming
SNARE complex has formed; synaptotagmin (v-SNARE) is brought to Ca2+ channels.
115
synaptotagmin is what
vSNARE
116
for fusion, wha triggers NT release
Ca2+
116
117
for fusion, Ca2+ binds to what
synaptotagmin
118
what does synaptotagmin do in fusion
embeds in membrane
119
vesicle membrane fuses with what
axon plasma membrane
120
is Ca2+ sufficient or necessary for vesicle fusion
necessary
121
what can disrupt vesicle fusion
some bacterial neurotoxins
122
2 main toxins that can disrupt vesicle fusion
BoTX and TeTX
123
what is BoTX
botox
124
what is TeTX
tetanus toxin
125
what happens to vesicles after they're used
they're repurposed -> recycle to endoscopes or are directly refilled
126
vesicles fusion increases membrane what (2 things)
surface area, capacitance
127
what does clathrin coat allow
endocytosis of vesicles
128
what does dynamin do
cleaves off vesicles and clathrin coat is removed
129
vesicles bound to actin filaments by what
synapsin
130
vesicles stored near what , but what
active zone, not available to fuse
131
release from reserve poll requires what
Ca2+
132
Ca2+ in reserve pool activates what
calmodulin
133
calmodulin activates what
calmodulin kinase II
134
CaMKII phosphorylates what , doing what
synapsin, releasing vesicles
135
for vesicular life style, what helps get to presynaptic membrane
Rabs
136
for vesicular life cycle, what binds what and what for docking
synaptobrevin binds SNAP 25 and syntoxin
137
for vesicular life cycle, what is ready to sense Ca2+
synaptotagmin
138
for vesicular life cycle, synaptogen binds what for fusion and NT release
Ca2+
139
which two things are involved in vesicular endocytosis and recycling
clathrin and dynamin
140
which pool is either being refilled or processed at endoscopes
recycling pol
141
reserve pool bound by what to actin filaments
synapsin
142
Chemical signal released by presynaptic neuron into synaptic cleft.
Neurotransmitters
143
neurotransmitters may cause response in what
psot synaptic neuron
144
describe postsynaptic responses from a NT
highly variable
145
NT responses occur thru activation of what
transmembrane receptor proteins
146
NT activation can cause what
postsynaptic changes to biophysical properties and synaptic efficacy
147
example of what can change for synaptic efficacy
quantal size
148
5 stages of NTs life
1) Synthesis
2) Packaging
3) Release into synaptic cleft
4) Binding of target receptors
5) Removal from synaptic cleft
149
three rules of classical NTs
Synthesized & loaded into vesicles by specific vesicular transporters for quantal release
Target specific receptors
Removed by specific enzymes
150
precursor for classical NT accumulated from where e
external enviroment
151
what is synthezied from the precursor
transmitter
152
well known classical NT
glutamate
153
transmitter packaged into vesicles by specific enzymes called what
transporters
154
what packages glutamate
VgluT
155
transporters exchange NTs for what
other molecules alone a gradient across vesicle membrane
156
what kind of molecules do transporters exchange NTs for
H+, K+, OH-
157
what happens when vesicle fuses with membrane
NT released
158
NT effect depends on what
target receptor
159
glutamate can be excitatory or inhibitory depending on what
receptor type
160
NTs removed from what in how many possible ways
synaptic cleft, 3 ways
161
3 ways NTs are removed from synaptic cleft
Transmitter broken down in synapse by metabolizing enzymes.
Transmitter taken up by glial cells for metabolic inactivation and recycling.
Transmitter directly recycled by the presynaptic cell.
162
what are used for bringing NTs back into cell
unique transporters
163
using glutamate example, what helps with uptake into vesicles
VGluT
164
using glutamate example, what uptakes into the cell
excitatory amino acid trasnporter
165
3 main families of classical NT
acetylcholine, glutamine derivatives, biogenic amines
166
what was first described NT
acetylcholine
167
acetylcholine is often...
excitatory
168
where is acetylcholine released at
NMJ and many central synapses
169
Ash synthesis enzyme and function
choline acetyltrasnferase, produces ACh from acetyl CoA and choline
170
where is choline found
mitochondria
171
ACh packaging enzyme
VAChT (vesicular Acetylcholine transporter)
172
describe ACh release and binding
they bind specific receptors
173
ACh removal reuptake enzymes and function
- Acetylcholinesterase - breaks down ACh into acetate and choline
- Na+/choline transporter - recycles ACh and brings it back into neurons
174
2 main glutamine derivatives
glutamate and gamma-amino butyric acid
175
glutamate type
excitatory or inhibitory
176
GABA type
inhibitory
177
glutamate synthesis enzyme and function
glutaminase produces glutamate from glutamine
178
glutamate packaging enzyme
VGluT (vesicular glutamate transporter)
179
glutamate release and binding
binds specific recepotrs
180
glutamate removal and reuptake enzymes and function
EAAT - (excitatory Amino acid transporter) brings glutamine into glia/neurons
- Glutamine synthetase recycles glutamate -> glutamine
181
GABA synthesis enzyme and function
Glutamic acid decarboxylase converts glutamate to GABA
182
GABA packaging enzyme
VIAAT (Vesicular Inhibitory Amino Acid Transporter)
183
GABA release and binding
binds specific receptors
184
GABA removal/ reuptake enzyme and function
GAT (GABA Transporter) brings GABA into glia/neurons
GABA aminotransferase recycles GABA glutamate
185
where does GABA aminotransferase work at
mitocondria
186
biogenic amines are all derivatives of what
amino acids
187
biogenic amines are all packaged into vesicles by what
VMAT (vesicular monoamine transporter)
188
biogenic amines are all broken down by what
MAOs (monoamine Oxidases)
189
distant features of biogenic amines are what
unique transporters for reuptake, some have extra degradation enzymes that are unique to them
190
DA abbreviation for
dopamine
191
NE abbreviation for
Norepinephrine (noradrenaline)
192
Epi is abbreviation for what
epinephrine (adrenaline)
193
5-HT is abbreviation for what
serotonin
194
HA abbreviator what
histamine
195
Pathway from tyrosine to epinephrine
tyrosine to DOPA to dopamine to norepinephrine to epinephrine
196
enzyme for tyrosine to DOPA
tyrosine hydroxylase
197
enzyme for DOPA to dopamine
DOPA decarboxylase
198
dopamine to norepinephrine enzyme
dopamine beta hydroxylase
199
norepinephrine to epinephrine enzyme
phenyl ethanol-amine N methyl trasnferase
200
neurotransmitters that include dopamine, norepinephrine, and epinephrine
catecholamines
201
catecholamines all derived from what
tyrosine
202
catecholamines all broken down by what
MAOs
203
cocaine blocks what
DA reuptake
204
more DA in synaptic cleft means what
enhances signaling
205
serotonin derived from..
tryptophan
206
serotonin derived from tryptophan which is catalyzed by...
2 enzymes
207
process from tryptophan to serotonin
tryptophan to 5-hydroxytryptophan to serotonin
208
enzymes on serotonin formation
tryptophan to 5hydroxytryptophan uses tryptophan-5-hydroxylase,....
5hydroxytryptophan to serotonin uses aromatic l-amino acid decarboxylase
209
serotonin broken down by what
MAOs plus a special serotonin acetyl transferase
210
histamine derived from ..
histidine
211
histamine broken down by...
MAOs and special histamine methyltransferase
212
enzyme for histamine to histamine
histidine decarboxylase
213
Many neurons release multiple NTs =
co release
214
describe co transmission
one cell with > 1 transmitter,
each vesicle = 1 transmitter type
215
describe vesicular energy
one cell with > 1 transmitter,
each vesicle > 1 transmitter type
216
5 states of NT lifecyce
synthesis, packaging, release, binding, removal
217
most classical NTs are derived from..
amino acids
218
3 classica NT families
ACh, glutamine derivatives, biogenic amines
219
difference between cotransmission vs vesicular synergy
co transmission = each NT type has its own vesicles
synergy = vesicles hold multiple NT types
220
categories of non classical transmitters
gaseous transmitters, peptide transmitters, endocannabinoids or lipid transmitters
221
can pass directly through plasma membrane.
gaseous transmitters
222
do gaseous transmitters require specific transmembrane proteins
no
223
can gaseous transmitters be stored in vesices
no
224
do gaseous transmitters need a specific receptor
no, can affect cellular signaling
225
example of gaseous NT
Nitric oxide
226
what activates NOS
Ca2+
227
what is NOS
nitric oxide synthase
228
NOS does what
converts arginine to NO
229
once NO diffuses, it activates what
soluable guanylyl cyclase
230
sGC produces what
cGMP
231
what does cGMP do
affects downstream targets in pre or postsynaptic cell and glia
232
how is reciprocal signaling used for NO
NO can be produced by pre or post synaptic cell
233
describe NO breakdown
passive, decays over time with no specific enzyme
234
How does NO break classical NT rules?
breaks all rules, cannot be contained in vesicle, no specific receptor, not degraded by a specific enzyme
235
peptide transmitters aka
neuropeptides
236
peptide transmitters are important for what
neuromodulation
237
what are neuropeptides
small sequences of amino acids that vary in length
238
peptide transmitters first synthesis step
precursors are syn in soma
239
neuropeptides synthesis step 2
packaged in the Golgi apparatus into vesicles
240
neuropeptides synthesis step 3
vesicles are transported to presynaptic terminal by axoplasmic transport
241
neuropeptides synthesis step 4
pro peptides are converted to neuropeptides en route to the terminal
242
neuropeptides synthesis step 5
released at synapse, but not quantal
243
neuropeptides and NT both generated where
in the soma
244
Peptidergic vesicles have low binding affinity for
Ca2+
245
describe AP need for neuropeptides
more APs are needed
246
describe neuropeptide breakdown
Broken down by various, non-specific proteolytic enzymes
247
do neuropeptides have reuptake transporters
no
248
Pre-propeptide processing is what
has signal peptide targeting for secretion
249
what is a propeptide
several neuropeptides
250
peptide capable of activating a receptor
active peptide
251
Neuropeptides are broken down by ...
peptidase enzymes
252
peptidase enzymes cleave between what
specific amino acids
253
are peptidase enzymes specific
not specific for a given neuropeptide
254
How do neuropeptides break classical NT rules?
no specific enzymes for breakdown
255
Lipids that pass directly through plasma membrane with no vesicular storage
endocannabinoids
256
lipid transmitters activate what
presynaptic receptors
257
which receptor is best known in the CNS
CB-1
258
in end cannabinoid synthesis and release , post synaptic Ca2+ stimulates what
PLC
259
PLC converts what to what
IPs to DAG
260
DAGL converts what to what
DAG, 2-AG,
261
what does 2-AG do
it diffuses and binds CB1 receptors
262
CB1 activation reduces what
local presynaptic vesicle release
263
2AG broken down by..
specific lipases
264
cannabinoids decrease what
transmitter release
265
CB1 receptors cause decrease in what
Ca2+ current which causes decrease in vesicular release
266
Effects of endocannabinoids depends on
presynaptic trasnmitter
267
What are some differences between endocannabinoids & the other two non-classical NTs: peptide & gaseous transmitters?
it Is broken down by specific enzymes; they have specific receptors, they act in retrograde
268
neuropeptides stored in what vesicles
peptidergic
269
2 major receptor types
ionotropic receptors, metabotropic receptors
270
inotropic receptors are what
ligand gated ion channels
271
metabotropic receptors are what
G protein couple receptors
272
receptor type with multiple subunits
inotropic
273
for singular subunits on inotropic receptors, what forms ligand binding site
n terminus
274
remainder of singular SU spans what how many times
membrane 3-4x
275
many subunits come together to create complete what
receptors
276
how can receptors have different properties
different subunits
277
what makes snake venom venomous
venoms contain compounds that target certain receptors
278
what receptor does snake venom mainly target for the NS, what does it regulate
nAChRs, regulate neuromuscular functions related to contraction, breathing
279
receptor with all the same subunits
homomeric receptor
280
describe opening for ionotropic receptors
direct opening, short latency and duration, makes for a rapid response but short lived
281
are inotropic receptors selective for ions, describe vm
yes, vm is biased toward Eion
282
Erev is what
Vm at which a neurotransmitter elicits no net current
283
if post synaptic potential hyper polarizes, describe post synaptic current
it increases
284
Vm approaches Erev regardless of what
start point
285
current does what with distance from Erev
increases
286
GABA a receptors are what
inhibitory, ligand gated Cl- channels that bias Vm to ECl-
287
GABA receptor activity causes what
shunting inhibition
288
for shunting inhibition, when permeability to Cl- increases, what happens
any inward current is shunted out of the neuron, which is reducing the depolarizing effect
289
nicotinic ACh receptors are what
primarily excitatory, ligand gated Na+/K+ channels that bias Vm to somewhere between ENa+ and EK+
290
describe ionotropic glutamate receptors
primarily excitatory, can be inhibitory, they're gated channels that differ in ion selective permeability
291
two channels of ionotropic glutamate receptors
AMPA and NMDA
292
AMPA binds what
glutamate directly, fast transmission
293
NMDA requires what
glutamate + secondary agonist = slow transmission
294
Receptor that is voltage and double ligand gated
NMDA
295
NMDA receptors have binding domains for what, which is what
glycine, co-agonist with glutamate
296
NMDA receptors have what binding sites, do what
Mg2+ binding sites, prevent ion flow
297
depolarization displaces what
Mg2+
298
inotropic receptors are what ion channels = what
ligand gated ion channels = short latency and duration
299
Vm where ionotropic receptor opening evokes no net current
Erev
300
what channels allow shunting inhibition
Cl-
301
for ionotropic glutamte receptors, faster, permits Na+ inside only
AMPA
302
for ionotropic glutamate receptors, slower, permits Na+ and Ca2+, voltage and double ligand gated
NMDA
303
GABA a is what kind of channel
Cl-
304
synapse the elicits effects in about 1 ms
direct
305
synapse that elects effects in about 100 milliseconds
indirect
306
ionotropic receptors have what kind of synapse
direct
307
metabotropic receptors have what kind of synapse
indirect
308
GPCRs have how many TM domains
7
309
G proteins are made of what
trimers
310
trimers are made up of what
subunits, alpha, beta, gamma
311
what can subunits of trimers do
directly or indirectly influence ion channels
312
alpha, beta, and gamma activate what, which is primary mediator
intracellular cascades, alpha
313
what is the process for alpha beta and gamma activating intracellular cascades
ligand binds, alpha beta and gamma dissociate, but beta and gamma remain together, they target different proteins
314
a single NT can activate what receptors, what's an example
ionotropic and metabotropic, ACh
315
describe receptor subtypes
many different metabotropic receptors for each transmitter, for each receptor class there are many receptor subtypes
316
once a G protein is activated, what can happen to open an ion channel
G protein activates, effector protein produces a second messenger that acts as a ligand to open the gated channel, increasing current from ion
317
activation of G proteins can cause changes in what channel properties
speed of gating, affinity of inactivation particles, pore diameter
318
what role does G protein activation play on gene expression
they can activate proteins that lead to gene expression changes, leads to changes in ion channel synthesis
319
4 methods of GPCR inactivation
receptor desensitized due to GTP hydrolysis , receptor sequestration, receptor degradation, arresting inhibition
320
receptor can be desensitized due to
GTP hydrolysis
321
describe receptor sequestration
agonist binds an endosome, deactivates receptor
322
describe receptor degradation
fuses with a lysosome which inactivates it
323
describe arrestin inhibition
when β-arrestin binds to an activated, phosphorylated GPCR and blocks its ability to activate G proteins — without necessarily removing the receptor from the cell surface yet.
324
7TM GPCRs and slow-acting relative to ionotropic receptors.
metabotropic receptor
325
G proteins affect what
channel function, vesicle release, transcription
326
receptors transfuse signals across the
membrane
327
in which receptor type is the signal fastest
direct, ionotropic
328
in which receptor type is the signal the slowest
indirect w second messenger, metabotropic receptor
329
2 ways that G proteins can act
directly or indirectly with second messengers
330
describe human G protein subunits , what does that mean?
20 alpha, 6 beta, 3 gamma, means lots of combinations which allows for lots of functions
331
1 NT being bound to a G protein can allow what
multiple G proteins to be effected
332
list the G alpha subtypes
Gs, Gq, Gi, Go
333
Gs function
increase adenylyl cyclase activity, which activates protein kinase A
334
Gq function
increase phospholipase C activity which increases intracellular Ca2+, increasing APs and Vesicle release
335
Gi function
decrease adenylyl cyclase activity
335
Go function
decrease intracellular Ca2+
336
intracellular singalling pathway
NT binds receptor, that activates G protein, that activates an effector protein, which deal with second messengers and then later effectors, which then take care of the target action
337
intracellular signalling is what and what does that mean
-is integrated, means it has to have a way to turn signaling off or reverse it
-is summated, means one receptor can cause lots of amplification
338
receptor to G proteins is there amplification
yes
339
G proteins to adenylyl cyclase is there amplificiotn
no
340
adenylyl cyclase to cyclic AMP is there amplification
yes
341
cyclic AMP to protein kinases amplification
no
342
protein kinases to phosphates that are transferred to target proteins is there amplification
yes
343
3 2nd messenger systehms
Cyclic nucleotides (cAMP + cGMP)
Inositol triphosphate (IP3) / diacylglycerol (DAG)
Calcium
344
what are the cyclic nucleotides
cAMP and cGMP
345
what does adenylyl cyclase produce
uses ATP to make cAMP
346
what inactivates cAMP
cAMP phosphodiesterase
347
cAMP activates what
cyclic nucleotide gated channel or protein kinase A
348
guanylyl cyclase produces what
cGMP from GTP
349
what deactivates cGMP
cGMP phosphodiesterase
350
cGMP does what
activates cyclic nucleotide gated channel and protein kinase G
351
PKA and PKG do what
phosphorylate nucleic transcription factors
352
what can increase the activity of adenylyl cyclase
Gs alpha
353
what activates PLCs
G proteins
354
class of membrane enzymes that cleave phospholipids just before the phosphate group
PLCs
355
PLC hydrolyzes what
PIP2
356
where is PIP2
in the membrane
357
hydrolysis of PIP2 causes what
IP3 to be released from membrane
- creates DAG
358
DAG and IP3 are both what
2nd messengers
359
IP3 triggers release of what from what, how
Ca2+ release from ER by binding IP3 receptors
360
DAG triggers activation of what
protein kinase C
361
many NTs, hormones, and other molecules can activate what, leading to what
PLC, leading to increased IP3 and/or DAG activity
362
Ca2+ comes from what 2 sources
ER and ion channels
363
Ca2+ activates what
calmodulin
364
ubiquitous protein with 4 calcium binding sites
calmodulin
365
what are the ways that Ca2+ can come from ion channels
exchanges (use conc grad), pump (uses energy), voltage and ligand gated channels
366
describe calmodulin targets
many targets like adenylyl cyclase, NOS, CaM kinase II, cyclic nucleotide phosphodiesterase
367
Think about cyclic nucleotides and IP3/DAG and how they fit into the framework to the right.
How does Ca2+ compare? What is the major difference?
Ca2+ acts only as a second messenger
368
what is neuromodulation
changing protein production of the cell
369
neuromodulation changes what
how neurons respond and communicate
370
how does neuromodulation change how neurons respond
changes biophysical properties (Rm)
371
how does neuromodulation change how neurons communicate
changes quantal content
372
membrane channel phosphorylation impacts what
channel kinetics and voltage sensitivity, combined affects Rm
373
Rm represents what
how excitable is this neuron
374
Applying 5-HT makes it easier to stimulate more APs by decreasing IK+ - how?
serotonin is increasing resistance, harder for membrane to depolarize, increases excitability
375
Neuromodulators also affect vesicle release without affecting
excitability
376
quantal content (m) =
available vesicles (n) X probability (p)
377
what can alter both n or p
neuromodulation
378
Intracellular signaling =
receptor > G-protein > effector protein > 2nd messenger > late effector > target action
379
Major 2nd messenger pathways
Ca2+, cyclic nucleotides, and IP3
380
GPCRs provide ..
amplification, flexibility and long-lasting effects
381
Neuromodulation affects
biophysical properties (ΔRm) or synaptic properties (Δm=p*n)
382
broad description of an electrical synapse
current flows directly into postsynaptic neuron, evoking response
383
is electrical synapse reversible
no
384
Networks of neurons are defined by
chemical and electrical connectivity
385
electrical synapses are defined by what
closer contact between the neurons as well as fewer docked vesicles
386
closer contact of electrical synapses is established by what
gap junctions
387
junctions are comprised of what
100s-1000s of connexions
388
each gap junction acts as what
channel connecting two cells
389
what is a connexon
TM protein that physically connects 2 cells
390
what builds 1 connexon complex
6 connexin subunits
391
what kind of channels are connexons
gated channels
392
many connexin subtypes combine why
to build unique connexons
393
connexin vs connexon
connexins make up connexons
394
connexon made up of identical connexins
homomeric
395
A connexon made of different connexins
heteromeric.
396
2 homomeric connexons are what junction type
homotypic
397
two opposite homomeric connexons are what junction type
heterotypic
398
two heteromeric connexons are what junction type
heterotypic
399
in gap junctions, junctions are made of what 2 components
pairing pr pre / post synaptic connexons
400
ion flow across the junction is what
instantaneous
401
features of electrical signals are what
transmitted with high fidelity( not as random), does not invert signal like chemical signals can
402
what kind of cells use this electrical signal
cells that need to fire together like cardiac muscle
403
2 consequences of electrical signaling
synchronized firing, spatial summation
404
what is a coupling ratio
degree to which vm in one neuron affects the other neuron
405
coupling ratios are always what
less than 1
406
16mV step in neuron “B64” = 1.6mV step in neuron “B71”... what is coupling ratio
.1
407
why do some electifcal synapses not equally reciprocal
cells have different connexon properties, different intrinsic properties
408
how can different intrinsic properties affect current thru junctions
cells with different resistance = same current will produce different voltages
409
how can different connexon properties affect current thru junctions
asymmetry in directional conductance
410
what will vary thru different connexons
conductance
411
what channels will have more symmetrical conductance between the two cells.
homotypic
412
Heterotypic channels will have more what
unidirectional conductance
413
describe transmission mechanism of electrical synapse
direct flow of ions thru gap junctions between cell
414
describe signal of electrical synapse
electrical signals (ions)
415
speed of electrical synapse
virtually instantaneous; no delay
416
direction of electrical synapse
bidirectional ( can flow in both directions.
417
direction of chemical synapse
unidirectional (presynaptic to post synaptic
418
modulation of electrical synapse
not modifiable, cannot convert excitatory to inhibitory
419
modulation of chemical synapse
highly modifiable, can convert excitatory to inhibitory signals
420
electrical synapse gap
very narrow gap, cells are physically connected by gap junctions
421
chemical synapse gap
large synaptic cleft
422
which is more reliable electrical or chemical
electrical
423
which can amplify signals electrical or chemical
chemical
424
Neurons can be electrically coupled via
gap junctions
425
hexameric proteins that form an ion channel
connexons
426
what makes up a connexon
6 connexins
427
Coupling ratios depend on
direction of current flow
428
coupling ratios affected by
connexin type and neuron properties
429
Electrical coupling can coordinate groups of neurons to elicit synchronized spikes and result in
spatial summation
