action potentials Flashcards
what are some passive membrane properties versus active membrane properties?
passive = - capacitance - time constant - length constant active = - VG ion channels - act pot
what is capacitance?
when two conducting materials are separated by an insulating material (lipid membrane in neurons)
stores charges of opposite sign on its two opposing surfaces
what determines the amount of charge stored by a capacitor?
inversely proportional to the thickness of the capacitor
what is the capacitive current?
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
what is the membrane time constant?
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
what is temporal summation?
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
what are cable properties of axons and dendrites?
have many of the same electrical properties of cables
includes passive spread of current and voltage changes along and axon or dendrite
what is the length constant?
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)
what is the speed of propogation?
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
what is the overshoot?
when the membrane potential becomes positive during the peak of an action potential
describe the activation and deactivation of Na versus K channels.
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
what happens during the rising phase of the action potential (in terms of channels and current)?
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
what determines the time course of an action potential?
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!
describe the falling phase of an action potential
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
what is the threshold potential?
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
what is the absolute refractory period?
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
what is the relative refractory period?
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
what are the general features of VG ion channels?
4 homologus domains
6 transmembrane regions
have pore loops between domains
what is the role of pore loops in VG ion channels?
ion selectivity - point into center of channel and create selectivity filter
how do channels select for specific ions?
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
what makes VG ion channels voltage sensitive?
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
what makes K VG ion channels close?
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)
what makes Na VG ion channels close?
have intracellular inactivation loop - string of positive proteins - flips up and inactivates the channel
how does the speed of activation of VG K, Na, and Ca channels compare?
Na is fastest, then Ca, then K is slowest
what’s the difference between T type and L type Ca channels?
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
how does norepinephrine affect Ca channels?
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
what is the role of the Ia K channel?
prolongs the interspike interval in cell that continuously fire act pot - slows depol of membrane so slows rate at which cell reaches threshold
what are hyperpolarization and cyclic nucleotide-gated channels (HCN)?
activated by hyperpolarization
open adn allow for cation influx => depolarization toward threshold
role in pacemaker activity of rhythmically active cells
how does lidocaine work?
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
what does use-dependent inactivation mean?
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
what are channelopathies?
disorders characterized by mutations in VG ion channels that result in abnormal ion channel activity and neuronal excitability
what mutation can be found in some epileptics and what is the result of this mutation?
can result in incomplete Na channel inactivation, prolonged depolarization, and abnormal electrical activity
how does the action potential travel down an axon?
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
what is the axon hillock (aka axon initiation segment = AIS)?
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
why don’t action potentials travel back up an axon (meaning why do they only travel in one direction/why are action pot unidirectional)?
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
what is myelin made of? how does it form?
tightly packed layers of gilal cell membrane wrapped around the axon
in PNS - leading edge of schwann cell wraps around
what does myelin do for axonal signaling?
decreases capacitance of the axon membrane (also somewhat increases membrane resistance)
=> longer length constant and higher conduction velocities
where does myelin come from in the CNS and PNS (think cell type)?
oligodendrocytes in CNS
one oligo can myelinate multiple axons
in PNS, schwann cells - one axon per cell
50% of cells in PNS myelinated
what are node of ranvier?
gaps in myelination along axons
have high concentration of VG Na channels
what does neuregulin regulate?
the number of wraps in the myelin around axons
the more neuregulin, the more wraps
what are some myelin-specific proteins and what do they do?
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
what is saltitory conduction?
when the action potential leaps from node to node as it moved down the axon
occurs because of myelination
what is guillain-barre syndrome?
loss of myelin in the PNS in some patches/spots - so focal
what is multiple sclerosis? what causes it? who is most likely to get it?
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
what are myelin plaques? in what patients would you expect to see them?
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
