Exam 2: Ch 6 Notes Flashcards
graded potential
size changes
curent decays over distance
how to improve loss of current
decrease resistance of cytoplasm (squid giant axons have large diameters for this)
increase membrane resistance (glial cells myelinate axons)
current decay w/ distance
length constant (measure of distance you move along axon when current is 37% of original)
record voltage change
indicator of how well current moves along axon/how badly it leaks out
what affects length constant
glial cells myleinate axons to inc length constant
squid giant axons inc diameter to inc length constant
what does it mean for an AP to be regenerative
current does not decrease w/ distance
voltage-gated channels drive the AP all along the axon
moves in 1 direction (cell body –> periphery)
if you artificially stimulate an axon in the middle…
AP goes both directions
cooling blocks the _____ of AP
conductance
speed of AP propagation
stimulate nerve at S1 and S2… measure time to contraction
speed differs in different neurons
cardiac AP
Na
voltage-gated Ca channels open (much longer inactivation)
delayed rectifier K channels
myelin sheath limits…
ions available on the extracellular side
solution: nodes of ranvier (tons of ion channels)
early symptoms of MS
blurred/double vision
clumsiness
thinking problems
loss of balance
numbness/tingling
2 types of synapses
electrical: direct coupling… very fast
chemical: indirect NT release, diffusion, bind receptors
modulation of 2 types of synapses?
electrical: not much
chemical: lots of scope
where are the biggest electrical synapses?
escape response
ex. crayfish escape response
glial cells have __ gap junctions
1/2
electrical synapses are…
specialized areas with lots of gap junctions
electrical connections, small ions and 2nd messengers
transmission of current has ______
resistance
reduced depol in post-syn cell… must be bidirectional
properties of electrical synapses
some have polarization
rectifying synapse works better in 1 direction than the other
AP in A drives AP in B, but AP in B does not drive AP in A
Charcot-Marie-Tooth disease (CMT)
slow progressive weakness/atrophy in distal leg muscles
> 400 mutations in gene coding for GJ protein connexin 32
GJs in peripheral and central myelinating cells play an important role in homeostasis of myelinated axons
stoke b/c glial cells can’t soak up excess nt
molecular biology techniques are used to study connexin roles
diff connexins have diff functions, if gene knocked out, different effects result
1st step in chemical synapses
AP in pre-syn cell reaches the terminal causing depol –> voltage-gated Na, K, and Ca channel open
Na moves in
Ca moves in
K moves out
2nd step chemical synapses
NT release (tightly regulated exocytosis) diffusion
if Ca removed extracellularly, no NT release
Conotoxin blocks…
Ca channels… no NT release
step 3 of chemical synapses
NT binds to post-syn receptor proteins; ion channels open
spte 4 of chemical synapses
NT removed from synaptic cleft (ex. ACh broken down by AChesterase), fused membrane is recycled
fast chemical transmission
vesicles are docked at active zones waiting for Ca inflow
slow chemical transmission
bigger vesicles/peptides
non-active zone release
G protein coupled receptor –> messengers
SNARES (proteins)
V-SNARE (vesicle) and T-SNARE (terminal active zone) are for docking
synaptotagmin
changes shape in presence of Ca
molecular handbrake
w/o Ca, vesicles docked
w/ Ca, vesicles touch membrane and release product
why did we study specialized synapses of the NMJ
extended and large synapses (easily accessible)
mitochondria - needs lots of energy
active zones –> multiple vesicles (pre-syn)
post-syn –> invaginations increase surface area for many receptors
why are the synapses of the NMJ specialized
1 pre-syn AP produces 1 AP in muscle
if measure close, theres a hump b4 AP
if measure further along, normal looking AP
synapse depol @ NMJ
ACh is released to nACh receptor
Na and K go through ACh receptor
toxin curare blocks ACh function
how to clamp voltage and measure current (muscle)
hold muscle membranes at set voltage initially by injecting current (control resting pot)
stimulate synapse
record changes in muscle voltage
reversal potential
the resting potential at which you get no change in voltage in the post-syn cell
no net driving force on ions so no net charge movement
reversal potential example
if channel is only permeable to Na and Na Eq pot = 65mV
if set resting pot is at 65 mV then when you stim the neuon, there is NT release and channels open but no change in muscle voltage
for 1 ion, _____ potential equals the reversal potential, for more than 1 ion it depends on…
Nernst
depends on [ ]s, and permeabilities of each ion
how can the same NT have a different effect on different cells
different receptors
nACh R @ NMJ vs. mACh R in the heart
nACh NMJ: excitatory, Na in K out, rest -70mV… depol
mACh heart: G-protein coupled, opens K channels, hyperpol, slow HR
in post-syn neuron, excitation vs inhibition
excitation: depol, Na and Ca
inhibition: hyperpol, K and Cl-; GABA –> influx of Cl- causes hyperpol
inhibition: depol w/ low Erev
do NT gated channels have specificity?
yes
epilepsy (seizures)
depol spreads to neighboring cells (focuses activity)
GABA meds stop spread to neighboring cells in adults
in kids: siezures got worse b/c meds drive depol (Cl- balance is opposite)
Cl- balance in adults vs kids
adults: low Cl- in cells
kids: high Cl- in cells
the ____, not ______ dictate excitation vs. inhibition
ions, channels
pre-syn inhibition
inhibiting neuron inhibits pre-syn neuron @ synapse (less nt release)
how much nt is released when no stimulation
tiny depols (mini endplate potentials)
caused by single vesicles losing control and releasing nt –> 0.1mV
tracking chemical synapses
Ca sensitive dye
voltage gated Ca channels –> synaptotagmin –> vesicle release
very fast change in [Ca]
CNS development has a different physiology than ____ CNS
mature
Retina: spontaneous Ca “waves” involved in establishing synapse connectivity
slow change in [Ca], spread via gap junctions
nt agonists
activate channels
nt antagonists
block/inhibit channels
vesicles have pumps in membrane to take in ___
ACh
what in addition to Sarin gas (nerve gas) can inhibit AChesterase
pesticides
NorEpi
reuptake pre-syn
broken down by MAO
recycled along w/ vesicles
why are NT recycled?
prevent rundown of available nt
membrane recycled
nACh R structure
5 subunits (2 alpha, beta, gamma, Y)
central pore w/ ACh sensitive open/close gating activity
neg charges inside channel, Na/K ions can pass
movement of Na/K through nACh R
Na in and K out
more Na moves b/c larger driving force –> depol cell
Beta subunit of nACh
4 transmembrane regions M1-M4
M2 lines the pore and imparts selectivity
where do you get enough ACh receptors to study?
torpedo electric ray
electroplaque
to open an ACh channel…
2 molecules of ACh needed b/c binds the 2 alpha subunits
change in conformation
patch clamp of ACh single channels
ACh inside electrode placed in denervated muscle fiber
denervation allows channels to inset along the whole muscle fiber
ACh binds –> channel opens –> inward current
ionotrophic glutamate receptor
M2 subunit doesn’t span membrane, but lines pore
provides selectivity
not all ACh receptors are ______
channels
mACh R
not a channel, G-protein coupled receptor
nt binds receptor and affects G-protein complex
G-protein affects the channel (voltage) and 2nd messengers and other cell functions
change in voltage for nACh vs. mACh
nACh: fast
mACh: slower
a G-protein can either do what to a channel
open or close a channel
ACh + leg muscle (nACh R)
depol
ACh + heart muscle (mACh R)
G-protein opens K channels –> hyperpol and slow HR
stimulating frog B cells pre-syn nerve gives multiple effects
1) fast EPSP when ACh binds nACh R (40ms)
2) slow EPSP with more stim when ACh binds mACh R (40s)
3) late, slow EPSP w/ diff receptor –> GnRH like peptide
slow EPSP
slow b/c G-protein is activated for longer
late, slow EPSP
late b/c NT comes from a nearby synapse and takes time to diffuse
slow b/c G-protein coupled
how does GnRH-like peptide cause depol
K channels normally open
G-prot mACh R + GnRH like receptors close channel
slow Na leak causes the depol
slow EPSP doesn’t drive AP, but…
makes more sensitive to input
depol 4mV so closer to threshold
shifts “resting” pot closer to theshold
key factors for multiple inputs on any dendrite
spread of depol from input PSP
density of receptors and channels
distance from spike initiating zone
1 more see PP
NMJ has what ratio input to AP
1:1
CNS APs
multiple small inputs sum to AP
depol or hyperpol (inhibit)
spatial summation
2+ inputs stimulated simultaneously onto same cell
adds together could be excitatory or inhibitory
temporal summation
same input –> multiple stim close in time occurs before 1st response has decayed
EPSP vs. AP
EPSP: change in voltage has a graded size
AP: threshold –> constant voltage
increasing stimulus size has what effect on the frequency of APs
increased frequency of AP
2 types of synaptic modulation
short term
long term
why is post-syn depol greater than summation? (EPSP)
b/c curare
Ca in nerve terminal after 1st stim
there is post-syn _______ and _______ after a short burst of high frequency stimulus
depression, potentiation
if normal stim + record (baseline) –> short tetanic stimulus –> normal stim + record………… what do you see?
depression followed by potentiation
in normal Ca… tetanic stim
depression b/c many vesicles released, which depletes vesicle store
pre-syn buildup of Ca (to release many vesicles) that the cell cannot buffer
in normal Ca….. delay tetanus
potentiation b/c excess Ca
in low Ca… tetanic stim
no depression
reduced vesicle release b/c low Ca, so no vesicle depletion
in low Ca…. delay tetanus
short potentiation
cell buffers Ca faster b/c low Ca
to test role of Ca in pre-syn nerve….
use a no Ca bath
heterosynaptic modulation
sensitization
one synapse alters function of a 2nd synapse by synapsing onto terminal
alters nt release by changing properties of 1st synapse
ex. serotonin alters channel kinetics of K channel
5HT receptor
G-protein coupled –> change in cAMP in 2nd synapse –> some K channels close (wider AP, lower depol, longer Ca influx, longer Ca release)
long term potentiation (LTP) / long term depression (LTD)
hippocampus
synapse strength –> nt glutamate
receptor types
AMPA: allows Na through, opens when glu binds
NMDA: allows Na + Ca through, opens when glu binds AND cell must also be depol
why does NMDA need depol?
Mg plug at resting pot, only removed by depol
how does Ca influx change synaptic strength?
increase AMPA # / decrease # AMPA receptors in post-syn neuron
LTP stimulates pre and post syn activity… how detect stimulus activity pre + post of single synapse?
pre: nt release; post: depol –> NMDA receptor –> molecular detector –> readout: change in Ca post-syn
changes AMPA receptor #
