03-20 APs; Myelin

Question 1

What is the relationship between the amount of charge stored and the thickness of the capacitor?

Answer 1

Inversely related: the thinner the capacitor, the more charge it can store

Question 2

What is capacitance current (Ic)?

Answer 2

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.

Question 3

What is ionic current (Ii)?

Answer 3

Ionic current occurs more and more as the buffering ability of the lipid bilayer “capacitor” is maxed out.

Question 4

What is the membrane time constant (τ)?

Answer 4

The amount of time needed for a neuron to be ~63% depolarized. Usually 1-10 msec in neurons.

Question 5

What is temporal summation?

Answer 5

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.

Question 6

Why do neurons exhibit cable properties?

Answer 6

b/c they have long axons each segment of which has its own internal resistance (r_i) and capacitance

Question 7

Length Constant: definition + equation

Answer 7

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

Question 8

Factors affecting the Speed of propagation

Answer 8

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.

Question 9

How can nematode have a nervous system that relies solely on passive spread of AP?

Answer 9

because it is only ~1mm long vertebrates need active properties of membranes to allow for more robust APs

Question 10

Define action potential

Answer 10

a quick depolarization and re-polarization in response to a membrane depolarization

Question 11

Na+ channel during AP

Answer 11

FIRST Na+ GOES IN -closed at RMP -opens when depolarized -then quickly inactivates -remains inactivated until repolarized

Question 12

K+ channel during AP

Answer 12

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

Question 13

What is the “threshold”?

Answer 13

-membrane potential where in the influx of Na+ > outflux of K+ -point of no return

Question 14

What is mechanism behind the refractory period?

Answer 14

-Na channels are inactivated -K channels are stil highly active

Question 15

What are the stages of the refractory period?

Answer 15

-absolute refractory period: cannot generate AP -relative refractory period: could elicit AP but need really high inward current

Question 16

What proportion of total Na, K an Ca ions in the immediate area actually move during an AP?

Answer 16

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

Question 17

What are the conserved features among voltage-gated ion channels?

Answer 17

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

Question 18

What confers selectivity on these ion channels?

Answer 18

-they’re able to sense the radius of the sphere of hydration surrounding an ion AND -the hydration energy

Question 19

What is structure involved in Na+ channel inactivation?

Answer 19

(+)’ly charged loop

Question 20

What is structure involved in K+ channel inactivation?

Answer 20

ball and chain

Question 21

T-type Ca channels?

Answer 21

“Transient”openings in response to depolarization; involved in “Transmitter” release) are found localized in the presynaptic terminal.

Question 22

L-type Ca channels?

Answer 22

“Longer-lasting channel openings in response to depolarization -mostly in cell body

Question 23

What is the Ca++ plateau? What cells use it?

Answer 23

cardiac cells and DRG neurons use Ca++ channels to slow the AP causing a plateau at the top of the AP spike

Question 24

What neurotransmitter can inhibit Ca++ channels and decrease the length of the plateau?

Answer 24

NorEpi via GPCRs

Question 25

delayed rectifier K channels

Answer 25

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

Question 26

I_A K channels

Answer 26

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?)

Question 27

HCN ion channel

Answer 27

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

Question 28

TASK K channels

Answer 28

the leaky K channels; help maintain the RMP

Question 29

f(x) of Voltage-gated Na+ channels in neurons

Answer 29

Prop of action potential

Question 30

f(x) of Voltage-gated Ca++ channels in neurons

Answer 30

Prop of AP; neurotrans release

Question 31

What are the different types of ion channels present on the neuron?

Answer 31

1. Leaky K+
2. Voltage-gated Na+
3. Voltage-gated Ca++
4. Delayed rectifier voltage-gated (non-inactivating) K+ channels
5. Voltage-gated (rapidly-inactivation/I_A) K+ channels
6. HCN (Hyperpolarization- and nucleotide-sensitive cation channels/I_h)

6.

Question 32

What are two natural poisons that affect Na+ ion channels? Mechanism of action?

Answer 32

Tetrodotoxin (from pufferfish) and saxitoxin (from red tide); block Na+ channel pores so that no ions can flow through

Question 33

What are conus toxins?

Answer 33

Made by fish-eating snails; inactivate Ca++ channels

Question 34

Lidocaine MOA?

Answer 34

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

Question 35

What’s a neuroma?

Answer 35

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.

Question 36

What is tetraethylammounium?

Answer 36

TEA blocks K+ channels; outward flow of K+ not seen when there is

Question 37

What prevents backpropogation of action potentials?

Answer 37

The absolute refractory period wherein the Na+ channels are inactivated and there is still some residual K+ channel activity.

Question 38

What is the mechanism by which myelin increases the speed of conduction?

Answer 38

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

Question 39

What is the range of nerve conduction velocities and which types of nerves are fastest?

Answer 39

1 to 120 m/s. The fastest are those neurons involved in proprioception.

Question 40

Compare and contrast Schwann and oligodendroglial cells?

Answer 40

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.

Question 41

What is unique about the membrane at the nodes of ranvier?

Answer 41

much higher [Na+ channel]

Question 42

What is signal to thickness of myelin sheath in PNS?

Answer 42

their thickness ends up being a constant ratio to axonal diameter; Neurregulin from the axon binds to ErbB on the Schwann cell

Question 43

What are the myelin membrane prots we need to know?

Answer 43

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

Question 44

Gullain-Barré Syndrome

Answer 44

PNS immune-mediated demyelination; rarely fatal

tx: IVIG or immunoglobulophoresis

Question 45

Multiple Sclerosis

Answer 45

CNS demyelination; relapsing/remitting types; vision is usally first to be affected; causes still unknown

one possibility: increased permeability of BBB to T-cells

Question 46

Charcot-Marie-Tooth Disease

Answer 46

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)