action potentials

Question 1

what are some passive membrane properties versus active membrane properties?

Answer 1

passive = 
- capacitance
- time constant
- length constant
active = 
- VG ion channels
- act pot

Question 2

what is capacitance?

Answer 2

when two conducting materials are separated by an insulating material (lipid membrane in neurons)
stores charges of opposite sign on its two opposing surfaces

Question 3

what determines the amount of charge stored by a capacitor?

Answer 3

inversely proportional to the thickness of the capacitor

Question 4

what is the capacitive current?

Answer 4

associated with the discharge or re-equilibration of the membrane capacitance
small, rapidly decaying current that is gradually replaced by the onset of ionic current flowing across the cell membrane
rapid and occurs in response to changes in membrane potential in either direction

Question 5

what is the membrane time constant?

Answer 5

approximately the length of time it takes for 63% of a change in membrane potential to occur
for most neurons, = 1-10 milliseconds
determines how close stimuli have to be for their membrane effects to sum to create an action potential - if the time constant is too short, won’t get summed depolarizations and so won’t ever reach threshold potential

Question 6

what is temporal summation?

Answer 6

when stimuli that are by themselves too small to elicit a large response overlap because the time constant is long enough - allows for combined influence - because if time constant is long, don’t fully recover from first stimuli before second stimuli

Question 7

what are cable properties of axons and dendrites?

Answer 7

have many of the same electrical properties of cables

includes passive spread of current and voltage changes along and axon or dendrite

Question 8

what is the length constant?

Answer 8

distance (in cm) at which 37% of the original change in membrane potential still occurs
so basically tells you how far down the axon a current can travel before being diffused across the membrane
will be greater if there’s better insulation (more myelin) along axon (just like a wire with thicker insulation will maintain a charge better than an uninsulated wire)

Question 9

what is the speed of propogation?

Answer 9

speed of the change in membrane potential traveling down an axon
know that it’s inversely proportional to 1/sq rt[(membrane resistance * internal resistance) * diameter]
larger diameter of axon = faster propagation

Question 10

what is the overshoot?

Answer 10

when the membrane potential becomes positive during the peak of an action potential

Question 11

describe the activation and deactivation of Na versus K channels.

Answer 11

Na channels are activated by membrane depolarization
deactivate rapidly even if the membrane continues to depolarize or remains depolarized

K channels don’t deactivate
open in response to depolarization but activate more slowly than Na channels

so both are opened by depolarization, but Na channels open right away, Na can flood cell and membrane can depolarize enough for act pot before K channels open to fix the change in potential

Question 12

what happens during the rising phase of the action potential (in terms of channels and current)?

Answer 12

currents through the V-G Na channels dominate
membrane depolarizes due to activation at the dendrite that is strong enough to depolarize the axon hillock
VG Na channels open and Na enters cell
VG Na channels automatically deactivate though
K channels open after a time delay, ending the rising phase

Question 13

what determines the time course of an action potential?

Answer 13

relative changes in the activity of VG ion channels

the Na/K pump does not play an important role in the time course of the action potential!

Question 14

describe the falling phase of an action potential

Answer 14

the Na channels have deactivated - they do so automatically after a certain period of time being open, even though the membrane is getting even more depolarized
after a time lapse, though, VG K channels open (these are different from the leak channels!)
this ends the rising phase and begins the falling phase, during which K exits the cell, which hyperpolarizes the membrane and returns it to it’s normal state
Na/K ATPases will then reestablish the proper concentrations

Question 15

what is the threshold potential?

Answer 15

usually around -40 mV in neurons
the point to which the membrane needs to be depolarized to trigger an action potential
balance tipped where you can’t go back

Question 16

what is the absolute refractory period?

Answer 16

from start of act pot to a little before the cell gets back to RMP (before relative refractory period)
can’t generate another act pot here because Na channels are still deactivated, so even if you re-depolarize the cell a lot, they can’t reopen yet

Question 17

what is the relative refractory period?

Answer 17

anther action potential can be started, but it takes a lot of depolarization - really large stimuli
because the cell hyperpolarizes - overshoots its correction to RMP and is more negative than the RMP for a while at the end of a act. pot.
it therefore takes a lot more stimulus - ie a larger depolarization - to get the threshold potential and trigger an action potential

Question 18

what are the general features of VG ion channels?

Answer 18

4 homologus domains
6 transmembrane regions

have pore loops between domains

Question 19

what is the role of pore loops in VG ion channels?

Answer 19

ion selectivity - point into center of channel and create selectivity filter

Question 20

how do channels select for specific ions?

Answer 20

selectivity filter in channels - created by pore loops
for size and for charge and for energy of hydration
smaller the ion, greater the energy of hydration

Question 21

what makes VG ion channels voltage sensitive?

Answer 21

probability of channel being open increases with increase in MP
there’s voltage sensor in the S4 region of the transmembrane region of these channels - full of positively charged AA - when membrane gets less negative, it repels that region and pushes that S4 region out (since positive things are repelled by other positive things)
these S4 regions are like cylinders in the TM region - they move up - it’s not understood how that relates to the opening of the channels, but if you remove them, the channels stop being voltage sensitive

Question 22

what makes K VG ion channels close?

Answer 22

inactivation “ball and chain”
each subunit has positively charged “ball” on end of “chain” of protein that’s in the cytoplasmic space - when the channel opens, the ball, since it’s positive, wants to leave the cell just like the K does - it tries to go through the channel, but doesn’t fit so it blocks it
only need one ball to plug channel, even though there’s 4 (one for each subunit)

Question 23

what makes Na VG ion channels close?

Answer 23

have intracellular inactivation loop - string of positive proteins - flips up and inactivates the channel

Question 24

how does the speed of activation of VG K, Na, and Ca channels compare?

Answer 24

Na is fastest, then Ca, then K is slowest

Question 25

what’s the difference between T type and L type Ca channels?

Answer 25

T-type usually found in synaptic terminals - transient

L-type are longer lasting - stay open for a little longer when opened - often in the cell body

Question 26

how does norepinephrine affect Ca channels?

Answer 26

binds to them and inhibits them => decrease in Ca influx in nerve terminal so decreased NT release
due to GPCR activation of a beta-gamma subunit via a second messenger mediated pathway

Question 27

what is the role of the Ia K channel?

Answer 27

prolongs the interspike interval in cell that continuously fire act pot - slows depol of membrane so slows rate at which cell reaches threshold

Question 28

what are hyperpolarization and cyclic nucleotide-gated channels (HCN)?

Answer 28

activated by hyperpolarization
open adn allow for cation influx => depolarization toward threshold
role in pacemaker activity of rhythmically active cells

Question 29

how does lidocaine work?

Answer 29

binds to the S6 region in the 4th domain of Na channels => use-dependent inactivation of the channel - keeps channel in inactivated state by stabilizing it

Question 30

what does use-dependent inactivation mean?

Answer 30

only blocks channels that were activated/open at the time of the use

so if want to target pain, the areas in pain will be activated and so will be affected by the drug, whereas other areas will not
so if there’s a low frequency of activation, won’t act on those cells

Question 31

what are channelopathies?

Answer 31

disorders characterized by mutations in VG ion channels that result in abnormal ion channel activity and neuronal excitability

Question 32

what mutation can be found in some epileptics and what is the result of this mutation?

Answer 32

can result in incomplete Na channel inactivation, prolonged depolarization, and abnormal electrical activity

Question 33

how does the action potential travel down an axon?

Answer 33

active properties of membrane generate initial action potential and then get passive spread of the potential along the axon - passive properties = when membrane depolarizes enough to open VG channels in axon membrane - usually at nodes of ranvier

Question 34

what is the axon hillock (aka axon initiation segment = AIS)?

Answer 34

an initial part of the axon with a high density of Na channels - often the site of action potential initiation

also serves as a barrier that restricts diffusion and spread of proteins between the axonal compartment and the somatodendritic compartment

Question 35

why don’t action potentials travel back up an axon (meaning why do they only travel in one direction/why are action pot unidirectional)?

Answer 35

the area that is closer to the axon hillock has just undergone an action potential and so is in refractory period, so it can’t create another potential. therefore, the flow of charge can only travel forward down the axon

if you were to depolarize an axon in the center of the axon, you would see the current flow in both directions, since none of the channels have entered refractory period yet

Question 36

what is myelin made of? how does it form?

Answer 36

tightly packed layers of gilal cell membrane wrapped around the axon

in PNS - leading edge of schwann cell wraps around

Question 37

what does myelin do for axonal signaling?

Answer 37

decreases capacitance of the axon membrane (also somewhat increases membrane resistance)
=> longer length constant and higher conduction velocities

Question 38

where does myelin come from in the CNS and PNS (think cell type)?

Answer 38

oligodendrocytes in CNS
one oligo can myelinate multiple axons

in PNS, schwann cells - one axon per cell
50% of cells in PNS myelinated

Question 39

what are node of ranvier?

Answer 39

gaps in myelination along axons

have high concentration of VG Na channels

Question 40

what does neuregulin regulate?

Answer 40

the number of wraps in the myelin around axons

the more neuregulin, the more wraps

Question 41

what are some myelin-specific proteins and what do they do?

Answer 41

P0 and proteolipid are each 50% of total protein in PNS myelin - help in compacting the myelin
myelin basic protein - in both CNS and PNS - membrane associated protein (not integral) - amphipathic - so has positive and negative side - likely also helps membranes get closer together
myelin associated glycoprotein - in both PNS and CNS - has large extracellular domain - only expressed on leading edge of myelin as it wraps around the axon - therefore likely involved in axon/glia recognition and initiation of the wrapping process

Question 42

what is saltitory conduction?

Answer 42

when the action potential leaps from node to node as it moved down the axon
occurs because of myelination

Question 43

what is guillain-barre syndrome?

Answer 43

loss of myelin in the PNS in some patches/spots - so focal

Question 44

what is multiple sclerosis? what causes it? who is most likely to get it?

Answer 44

loss of myelin in CNS
often get blurred vision, muscle weakness
autoimmune reaction to myelin - immune cell infiltration across BBB, T cells activate microglia and macrophages and myelin is
destroyed

most prevalent in northern scandinavian populations
low vitamin D may also contribute

Question 45

what are myelin plaques? in what patients would you expect to see them?

Answer 45

localized areas of myelin destruction - accumulation of macrophages, neutrophils and debris
appear as white spots on MRIs
see them in patients with MS and other disorders that involve destruction of myelin