03-20 APs; Myelin Flashcards
What is the relationship between the amount of charge stored and the thickness of the capacitor?
Inversely related: the thinner the capacitor, the more charge it can store
What is capacitance current (Ic)?
This is due to the rearranging of charges that occurs after an injection of charge. The capacitance buffers the incoming charge at a rate that is equivalent to the current of ions flowing in. **Causes a lag in the observed ∆membrane potential.
What is ionic current (Ii)?
Ionic current occurs more and more as the buffering ability of the lipid bilayer “capacitor” is maxed out.
What is the membrane time constant (τ)?
The amount of time needed for a neuron to be ~63% depolarized. Usually 1-10 msec in neurons.
What is temporal summation?
Temporal summation is when stimuli that are too small to cause a large response by themselves occur frequently enough that the cell doesn’t have time to depolarize and they begin to have an additive effect. This is based in part of the time constant of a particular cell.
Why do neurons exhibit cable properties?
b/c they have long axons each segment of which has its own internal resistance (r_i) and capacitance
Length Constant: definition + equation
distance in cm away from the origin of an AP at which only 37% of the original charge on the membrane remains λ = sqrt(r_m/r_i) λ is length constant r_m is membrane resistance r_i is internal resistance to current flow **usually 0.1-1.0mm
Factors affecting the Speed of propagation
inversely proportional to (the square root of): -r_m (memb. resist) —> (α 1/d) -r_i (int. resist. to flow) —> (α 1/d^2) -C_m (memb capacitance) —> (α d) ***d = diameter THE FUCKING POINT IS THAT AS AXON GETS WIDER SPEED GETS FASTER. DAMN.
How can nematode have a nervous system that relies solely on passive spread of AP?
because it is only ~1mm long vertebrates need active properties of membranes to allow for more robust APs
Define action potential
a quick depolarization and re-polarization in response to a membrane depolarization
Na+ channel during AP
FIRST Na+ GOES IN -closed at RMP -opens when depolarized -then quickly inactivates -remains inactivated until repolarized
K+ channel during AP
SECOND K+ GOES OUT **many types; more common “delayed rectifier” K channels: -activate in response to depolarization but slower than Na+ channels -stay activated, however -close once repolarized
What is the “threshold”?
-membrane potential where in the influx of Na+ > outflux of K+ -point of no return
What is mechanism behind the refractory period?
-Na channels are inactivated -K channels are stil highly active
What are the stages of the refractory period?
-absolute refractory period: cannot generate AP -relative refractory period: could elicit AP but need really high inward current
What proportion of total Na, K an Ca ions in the immediate area actually move during an AP?
a very small % of total ions actually move during AP; small amt of mov’t all that is needed to ∆ RMP —therefore, the Na+/K+ ATPase is not that important to AP generation
What are the conserved features among voltage-gated ion channels?
1) have 4 intracellular components each with 4-fold symmetry (or in the case of K channels, they are singular separate proteins each w/ just one channel, but you need for of them to localize together to work properly) 2) a narrow, ion-specific selectivity feature (“pore loops”) 3) they have voltage sensitive S4 regions 4) they have special inactivation loops
What confers selectivity on these ion channels?
-they’re able to sense the radius of the sphere of hydration surrounding an ion AND -the hydration energy
What is structure involved in Na+ channel inactivation?
(+)’ly charged loop
What is structure involved in K+ channel inactivation?
ball and chain
T-type Ca channels?
“Transient”openings in response to depolarization; involved in “Transmitter” release) are found localized in the presynaptic terminal.
L-type Ca channels?
“Longer-lasting channel openings in response to depolarization -mostly in cell body
What is the Ca++ plateau? What cells use it?
cardiac cells and DRG neurons use Ca++ channels to slow the AP causing a plateau at the top of the AP spike
What neurotransmitter can inhibit Ca++ channels and decrease the length of the plateau?
NorEpi via GPCRs
delayed rectifier K channels
These do not have a ball-and-chain and therefore do not inactivate but stay open for the full length of the depolarization. -The activate more slowly than Na+ channels prolly ‘cause their S4 region has one fewer +ly charged AA
I_A K channels
A Current K+ channels counteract depolarization; not enough of them to prevent an AP, but they slow its generation and then are responsible for lengthening the interspike interval (involved in refractory period?)
HCN ion channel
Hyperpolarization and nucleotide sensitive cation channels; mostly let Na+ in after hyperpolarization that results following the AP; creats I_h current; Sensitive to nucleotides like cAMP that allow this to be modulated by the cell’s metabolic state; important for rhythmically firing neuronal cells
TASK K channels
the leaky K channels; help maintain the RMP
f(x) of Voltage-gated Na+ channels in neurons
Prop of action potential
f(x) of Voltage-gated Ca++ channels in neurons
Prop of AP; neurotrans release
What are the different types of ion channels present on the neuron?
- Leaky K+
- Voltage-gated Na+
- Voltage-gated Ca++
- Delayed rectifier voltage-gated (non-inactivating) K+ channels
- Voltage-gated (rapidly-inactivation/I_A) K+ channels
- HCN (Hyperpolarization- and nucleotide-sensitive cation channels/I_h)
6.
What are two natural poisons that affect Na+ ion channels? Mechanism of action?
Tetrodotoxin (from pufferfish) and saxitoxin (from red tide); block Na+ channel pores so that no ions can flow through
What are conus toxins?
Made by fish-eating snails; inactivate Ca++ channels
Lidocaine MOA?
blocks Na+ channels in a use-dependent fashion; since pain neurons are firing more rapidly in the presence of a painful stimulus the drug becomes more effective under these conditions
What’s a neuroma?
tangle of swollen nerve fibers at the site of a severed nerve; increased concentration of Na+ channels in these areas leads to hyperexcitiability, phantom pain, etc.
What is tetraethylammounium?
TEA blocks K+ channels; outward flow of K+ not seen when there is
What prevents backpropogation of action potentials?
The absolute refractory period wherein the Na+ channels are inactivated and there is still some residual K+ channel activity.
What is the mechanism by which myelin increases the speed of conduction?
Myelin widens the “capacitor” aspect of the neuron (i.e. the separate of negative charge inside the cell from positive charge outside the cell). These decreases the resistance of the mov’t of Na+ during the propogation of an AP.
It does however slightly increases the membrane resistance
What is the range of nerve conduction velocities and which types of nerves are fastest?
1 to 120 m/s. The fastest are those neurons involved in proprioception.
Compare and contrast Schwann and oligodendroglial cells?
Both myelinate axons.
Schwann = PNS myelination; cells themselves (i.e. w/ their nuclei) wrapping the axons
Olgios = CNS myelination; extend anucleate processes from their cell bodies that myelinate up to 40-50 axons each.
What is unique about the membrane at the nodes of ranvier?
much higher [Na+ channel]
What is signal to thickness of myelin sheath in PNS?
their thickness ends up being a constant ratio to axonal diameter; Neurregulin from the axon binds to ErbB on the Schwann cell
What are the myelin membrane prots we need to know?
MBP: myelin basic protein; cytosol side, f(x) unknown maybe tight coiling?
MAG: myelin-associated glycoprotein; only in first wrap; prolly involved in recognition of neuron; looks like an Ig
P_o: structural prot in PNS myelin only
PLP: proteolipid protein; CNS version of P_o
Gullain-Barré Syndrome
PNS immune-mediated demyelination; rarely fatal
tx: IVIG or immunoglobulophoresis
Multiple Sclerosis
CNS demyelination; relapsing/remitting types; vision is usally first to be affected; causes still unknown
one possibility: increased permeability of BBB to T-cells
Charcot-Marie-Tooth Disease
Peripheral motor and sensory neuropathy; problems running, later hands lose mov’t and sensory problems
genetic; one of the most common neurogenetic dzs (1:2000)
