5- synap phys 1 Flashcards
AP Breakdown
What determines value of membrane potential
@ rest, what is concentration of K+ inside the cell vs outside
what about for Na+
relative permeability to different ions
@ rest, K+ high inside, low outside
@ rest, Na+ high outside, low inside
what is most excitable part of neuron
what is Vm at hillock?
What is threshold potential
axon hillock = junction of axon at cell body
Vm resting at hillock = -70
Vm at threshold = -55
what triggers the action potential
when depol bring Vm to threshold –> Na influx and K+ efflux balanced out
for a given length of axon, the intracellular resistance is (greater/lesser) than ECF resistance b/c
how do axons act like resistors
greater resistance b/c smaller area
ions keep leaking out after positive charges stop entering cell so less charge transmit
How do axons compensate for excess leakage of ions
VG Na channels sense decaying message –> energy source is Na gradient to inject extra + charge
AP shape is ___
sterotyped so same amplitude and time for all AP
Process of AP
1) depol Vm –> Na chnanel open
2) open K+ channels
3) Na channels close at peak of AP
4) K+ channels keep open causing hyperpol
Sodium channel activ and inactiv gate
at rest
as membrane depol
at peak of AP
as membrane repol
at refractory period
at rest = activ gate (m) closed and inactiv gate (h) open
as membrane depol = activ gate (m) open and inactiv gate (h) close (activ gate swing faster than inactiv gate)
at peak = activ gate (m) and inactiv gate (h) open
as membrane repol = activ gate (m) closing and inactiv gate (h) closed
at refractory period = activ gate (m) and inactiv gate (h) closed
What is absolute vs refractory period
absolute = no action potential fired
relative = need more extreme stim to fire
what is basis for refractory period
1) after axon repol, both activ (m) and inactiv (h) gate of Na channel closed (inactiv gate require time to reopen)
2) after axon repol, K+ still open so K+ leave clell and harder to depol
Define safety factor
motor terminal secretes few times more than minimum # of vesicles needed (impt in repetitive stim when # of vesicles exocytosis decr)
axons have more than minimal # of Na channels required for conduction of AP
How do you incr conduction velocity
1) bigger diameter
2) less leaky surface membrane
3) higher density of Na channels
what is cardiac AP plateau created by?
anomalous rectifier (K+ channel that close with depol) and voltage gated Ca2+ channel
What is electrical synaptic transmission
What is impt protein pore that connect cytoplasm of 2 adjacent cells
Also present where else for what reason
When elctric current spread from one neuron to another via gap junctions
have protein = connexin to allow small ions and molec to pass thru
also found in heart and smooth muscle where rapid transmission from once cell to another
what is limitation of electrical synaptic transmission? is it used in mammalian CNS?
can’t provide same amplification of signal that chemical synaptic transmission can (BOTH PRE AND POST SYNAP CELL NEED TO BE COMPARABLE SIZE) but presynap much smaller than postsynap so not used in CNS
NMJ depol works using chemical amplifier
what is mechanism
1) 1 vesicle = 2000 molec of ACh
2) ACh activ each ACh receptor
3) 1mV per ACh –> 1000 ACh = 1 uM
4) 1 uM x 1000 ACh receptor = 1 mV of depol per vesicle
5) 1 mV * 100 vesicle = 100 mV depol
What triggers NT release
1) AP arrive at motor nerve terminal
2) VG ca2+ open –> influx Ca2+
3) fuse vesicle membrane with nerve terminal membrane
4) vesicle exocytosis
5) ACh release from synap cleft
What is mech after ACh released into cleft
1) ACH binds ACh recpetor in muscle fiber
2) ligand gated channels open
3) Na+ flow into muscle fiber
4) muscle fiber depol to threshold
5) more VG ion channels open –> more Na open
6) 2 APs generated, travel in opposite direction
ACh receptor is a ___
nonselective cation channel
How does presynaptic cell return back to original state
1) Ca2+ ion pump out of nerve terminal
2) postexocytic synaptic vesicles retrieved
Kiss and run after 1 AP-
Full fusion exocytosis for more prolonged excitation
Describe mechanism of kiss and run to reset NT
1) vesicle membrane fuse with nerve terminal membrane but retain shape
2) dynamic snips and release vesicle near site of exocytosis
3) vesicle refilled with NT and ready for release
Describe mechanism of full fusion exocytosis to reset NT
1) vesicle membrane fuse with nerve terminal membrane but collapses into presynap membrane
2) clathrin coats vesicle membrane
3) dynamin snip and release clathrin coated vesicle
4) vesicle uncoat and refilled with NT
How does synaptic cleft return back to original state
3 mechanisms
1) Simple diffusion –> ACh diffuse out of synap cleft into high volume of surrounding medium
2) ACh esterase ***** = AChE tethered in basal lamina in synaptic cleft to eat up ACh
3) Reuptake = nerve terminal takes up cleavage products of AChE (choline) to resynth ACh
What is job description for motor nerve terminal
you must secrete enough ACh to depol the muscle fiber that you innerv to threshold for an AP
Acts as all or none switch
(When AP arrives you have to secrete ENOUGH ACh to depol membrane to reach threshold (~30 mV))
- -> too little = no twitch
- -> too much –> single twitch with wasted ACh
Why do you need to amplify signal?
How does NMJ synapse amplify incoming signal to depol muscle fiber to threshold?
b/c nerve terminal is much smaller than muscle fiber so can’t produce current
Depol by 30 mV then trigger chemical synapse (see other flashcard)
When does facilitation and synaptic depression occur?
during repetitive stimulation (lasts 0.1s until pump out Ca2+ from 1st AP)
usu simultaneous with facilitation first then depression (depression recovers in 5s)
Distinguish btwn facilitation and synaptic depression
facilitation = purpose to handle extra calcium entering cell with high freq stim (too much Ca2+, too many vesicles secreted)
synaptic depression = occurs due to depletion of releasable synaptic vesicles - can’t replenish fast enough
Define MEPPs
Distinguish from EPP
miniature end plate potentials =
spontaneous exocytosis of one vesicle
EPP = synch release of multiple MEPPs (50-100)
Define quantum hypothesis
NT secretion from integral number of multimolec packets
Define vesicular hypothesis
each quantum = contents of single synaptic vesicle
Define myasthenia gravis
what happens with repeated activity
ab against ACh receptors
decr MEPP and EPP amplitude
incr activity, synaptic depression decr quantal output –> weakness
define myasthenic syndrome (Lambert Eaton Syndrome)
what happens with repeated activity
ab against presynap calcium channel
incr activity, syanptic facilitation –> stronger (no depression b/c few vesicles exocytosis)
CMTX neuropathy mutation where?
treatment?
point mutation in connexin-32
tonabersat and derivatives (benzopyrans) (also used to decr migraines, seizures ***
Describe SNARE proteins
synaptobrevin
synaptotagmin
SNAP25 and syntaxin located where?
synatpobrevin = interact with corresponding molec in presynap membrane
synaptotagmin = calcium sensor
presynaptic membrane
syntaxin binds synaptobrevin
Mechanism of sarin, cyclosarin, tabun
cocaine
neostigmine
fluoxetine hydrochloride (Prozac)
block AChesterase (less likely than neostigmine to be turned on/off)
block reuptake of dopamine
block ach esterase and prolongs current at NMJ (used for myasthenia gravis)
SSRI
