5- synap phys 1

Question 1

AP Breakdown

What determines value of membrane potential

@ rest, what is concentration of K+ inside the cell vs outside
what about for Na+

Answer 1

relative permeability to different ions

@ rest, K+ high inside, low outside
@ rest, Na+ high outside, low inside

Question 2

what is most excitable part of neuron

what is Vm at hillock?
What is threshold potential

Answer 2

axon hillock = junction of axon at cell body

Vm resting at hillock = -70
Vm at threshold = -55

Question 3

what triggers the action potential

Answer 3

when depol bring Vm to threshold –> Na influx and K+ efflux balanced out

Question 4

for a given length of axon, the intracellular resistance is (greater/lesser) than ECF resistance b/c

how do axons act like resistors

Answer 4

greater resistance b/c smaller area

ions keep leaking out after positive charges stop entering cell so less charge transmit

Question 5

How do axons compensate for excess leakage of ions

Answer 5

VG Na channels sense decaying message –> energy source is Na gradient to inject extra + charge

Question 6

AP shape is ___

Answer 6

sterotyped so same amplitude and time for all AP

Question 7

Process of AP

Answer 7

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

Question 8

Sodium channel activ and inactiv gate

at rest

as membrane depol

at peak of AP

as membrane repol

at refractory period

Answer 8

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

Question 9

What is absolute vs refractory period

Answer 9

absolute = no action potential fired

relative = need more extreme stim to fire

Question 10

what is basis for refractory period

Answer 10

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

Question 11

Define safety factor

Answer 11

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

Question 12

How do you incr conduction velocity

Answer 12

1) bigger diameter
2) less leaky surface membrane
3) higher density of Na channels

Question 13

what is cardiac AP plateau created by?

Answer 13

anomalous rectifier (K+ channel that close with depol) and voltage gated Ca2+ channel

Question 14

What is electrical synaptic transmission

What is impt protein pore that connect cytoplasm of 2 adjacent cells

Also present where else for what reason

Answer 14

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

Question 15

what is limitation of electrical synaptic transmission? is it used in mammalian CNS?

Answer 15

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

Question 16

NMJ depol works using chemical amplifier

what is mechanism

Answer 16

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

Question 17

What triggers NT release

Answer 17

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

Question 18

What is mech after ACh released into cleft

Answer 18

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

Question 19

ACh receptor is a ___

Answer 19

nonselective cation channel

Question 20

How does presynaptic cell return back to original state

Answer 20

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

Question 21

Describe mechanism of kiss and run to reset NT

Answer 21

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

Question 22

Describe mechanism of full fusion exocytosis to reset NT

Answer 22

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

Question 23

How does synaptic cleft return back to original state

3 mechanisms

Answer 23

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

Question 24

What is job description for motor nerve terminal

Answer 24

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

Question 25

Why do you need to amplify signal?

How does NMJ synapse amplify incoming signal to depol muscle fiber to threshold?

Answer 25

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)

Question 26

When does facilitation and synaptic depression occur?

Answer 26

during repetitive stimulation (lasts 0.1s until pump out Ca2+ from 1st AP)

usu simultaneous with facilitation first then depression (depression recovers in 5s)

Question 27

Distinguish btwn facilitation and synaptic depression

Answer 27

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

Question 28

Define MEPPs

Distinguish from EPP

Answer 28

miniature end plate potentials =
spontaneous exocytosis of one vesicle

EPP = synch release of multiple MEPPs (50-100)

Question 29

Define quantum hypothesis

Answer 29

NT secretion from integral number of multimolec packets

Question 30

Define vesicular hypothesis

Answer 30

each quantum = contents of single synaptic vesicle

Question 31

Define myasthenia gravis

what happens with repeated activity

Answer 31

ab against ACh receptors
decr MEPP and EPP amplitude

incr activity, synaptic depression decr quantal output –> weakness

Question 32

define myasthenic syndrome (Lambert Eaton Syndrome)

what happens with repeated activity

Answer 32

ab against presynap calcium channel

incr activity, syanptic facilitation –> stronger (no depression b/c few vesicles exocytosis)

Question 33

CMTX neuropathy mutation where?

treatment?

Answer 33

point mutation in connexin-32

tonabersat and derivatives (benzopyrans) (also used to decr migraines, seizures ***

Question 34

Describe SNARE proteins
synaptobrevin

synaptotagmin

SNAP25 and syntaxin located where?

Answer 34

synatpobrevin = interact with corresponding molec in presynap membrane

synaptotagmin = calcium sensor

presynaptic membrane
syntaxin binds synaptobrevin

Question 35

Mechanism of sarin, cyclosarin, tabun

cocaine

neostigmine

fluoxetine hydrochloride (Prozac)

Answer 35

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