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Neurobiology > Exam I Review > Flashcards

Exam I Review Flashcards

1
Q

2 types of cells in the brain

A

Neurons - ~100b in the brain

Glia - 10-50x more glia

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2
Q

Neuron structure

A
  • Polarized (has different functional regions)
  • Divided into 4 anatomical/functional regions
    1. Dendrites
    2. Soma
    3. Axon
    4. Axon terminals
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3
Q

Functional neuron classification

A
  1. Sensory neurons (peripheral to CNS)
  2. Motor neurons
  3. Interneurons (largest #, most in brain, relay (projection)
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4
Q

Morphological neuron classification

A
  1. Unipolar (1 process)
  2. Bipolar (1 axon, 1 dendrite)
  3. Multipolar (1 axon, multiple dendrites)
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5
Q

DRG neuron

A

A special type of bipolar neuron (pseudo-unipolar neuron)

The stem axon separates into a peripheral and a central axonal branches

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6
Q

Neuronal Markers for parts of neuron

A

MAP2 - DENDRITES + SOMA
(NOT axons)

Tau - AXON

These proteins make excellent neural markers
==> can do double culture

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7
Q

Types of glial cells

A
  1. Microglia [clearing cells involved in disease, scavengers of the brain, pick up cell debris, activated after nerve injury]
  2. Macroglia
    (1a) Schwann cells [form PNS myelin]
    (2a) Oligodendrocytes [CNS myelin, single oligo can wrap around many cells]
    (3a) Astrocytes [most abundant in CNS, various functions]
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8
Q

Schwann cell

A

Speed up AP velocity

Very little cytoplasm, basically just a lipid bilayer

Form many, many layers around

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9
Q

Functions of glial cells

A

[Most abundant in brain, =/ glue, located b/w neurons fill up much of brain]

  1. Structural support
  2. Form myelin sheath
  3. Microglia = scavenge/cell debris clean-up
  4. Help neuronal signaling
    - - Don’t directly participate (no AP) but help maintain ionic conditions, buffer extracellular [K+], some astrocytes take up NTs
  5. Guide neuron migration and axon outgrowth
  6. Form BBB
  7. Release GFs to nourish nerve cells
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10
Q

Glial stem cells

A

oligo and schwann cells have stem cells
can regenerate

some astro

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11
Q

Neural communication

A

electrical + chemical

Chemical signal converted back into electrical
AP –> SP –> AP [synaptic potential]

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12
Q

Nernst equation

A

Tells you equilibrium potential of an ion

E = RT ln (ion)o
/zF /(ion)i

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13
Q

Equilibrium potential

A

When chemical gradient = electrical gradient

The membrane potential where net flow = 0

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14
Q

Hypothetical cell

  • Higher K inside
  • Channels closed
  • Then channels open, what happens?
A
  1. When closed - no membrane potential when equal #s of K+ and A- on each side
  2. Channels open
    K+ ions flow out due to concentration gradient
    Leaving behind negative charge
    (outside becomes more pos, inside becomes more neg)
    Then reaches equilibrium
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15
Q

GHK Equation

A

Calculates mem potential when multiple ions present
Resting membrane potential depends on GHK

Mem potential not governed by ion ion - it is established by the RELATIVE CONTRIBUTIONS of many

Equation

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16
Q

Na+

A

12 in, 145 out

More outside

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17
Q

K+

A

139 in, 4 out

More inside

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18
Q

Cl-

A

4 in, 116 out

More outside

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19
Q

Ca2+

A

0.1 micro in, 1.8 mm out

More out, but low overall (universal signaling molecule)

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20
Q

Mg2+

A

0.8 in, 1.5 out

More out

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21
Q

A-

A

138 in, 9 out

More in, very low out

A-: proteins, other organic molecules

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22
Q

RMP is most permeable to

A

K+
then Ca2+

Not Na+ though

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23
Q

What contributes to RMP?

A
  1. Leak K+ channels
  2. Nonselective cation channels
  3. Leak Na+ channels
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24
Q

What contributes to AP?

A

Voltage-dependent Na+ and K+ channels

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25
Q

Why do cells need ion potentials?

A
  • Too much ENERGY needed to move a monovalent ion from water to lipid
  • Ions are CHARGED so can’t go through hydrophobic lipid bilayer
  • According to BOLTZMANN distribution, probability of it happening is basically none
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26
Q

Essential properties of ion channels

A
  1. Membrane proteins
  2. Selectivity (recognize/select particular ions)
  3. Conduction (pass ions passively and rapidly - no energy needed bc going down concentration gradient)
  4. Gating (open/close in controlled fashion, according to intra/extra -cellular cues)
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27
Q

Roderick MacKinnon

A

Nobel prize for chem in 2003
Found structure of ion channels
worked with Kcsa K+ channel

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28
Q

Cryo-electronmicroscopy (Cryo-EM)

A

Historically low resolution, improved to high res in 2013

Allowed for many channels to be discovered

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29
Q

What allowed for many ion channels to be discovered?

A 
Roderick MacKinnon (first discovered ion channels)
Cryo-EM
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30
Q

NDMA receptor

A

Important for learning and memory

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31
Q

Why are ion channel structures important?

A
  1. Gain better understanding of how channels work
  2. Can map disease-causing mutations onto channels
  3. Can study drug molecules to design better meds
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32
Q

Classification of ion channels

A
  1. Based on SELECTIVITY
2. Based on GATING MECHANISMS
     voltage-gated
     ligand-gated (NTs)
     mechanically-gated
     temperature-gated
     gap-junctional channels (usually always open, but can be regulated; can allow ions and small molecules due to large pores)
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33
Q

Nonselective cation channels

A

Allow all POS ions to pass through

Typically K+ and Na+, sometimes Ca2+

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34
Q

Gating

A

Opening/closing of channel

Even LEAK CHANNELS can close

All ion channels go between these 2 states

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35
Q

4 ways to open/close a channel

A
  1. Voltage change (mostly opened by dep.)
  2. Ligand binding/unbinding
  3. Membrane stretch /mechanical force
  4. Temperature change
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36
Q

Inactivated state

A

Many channels have this stage

Allows AP to be unidirectional (refractory period)

I cannot be opened by stimulus

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37
Q

Tetrodotoxin

A

TTX

Puffer fish toxin

Na+ channel inhibitor

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38
Q

Saxitoxin

A

STX

Shellfish toxin

Na+ channel inhibitor

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39
Q

Tetraethylammonium

A

TEA

K+ channel inhibitor

Often used in research

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40
Q

Ba2+

A

K+ channel inhibitor

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41
Q

Dihydropyridines

A

Ca2+ channel inhibitor

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42
Q

Cd2+

A

Heavy metal

Ca2+ channel inhibitor

Many heavy metals can block channels

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43
Q

Curare

A

Blocks nicotinic ACh receptor on NMJ

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44
Q

β-bungarotoxin

A

Snake toxin

Blocks ACh receptor

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45
Q

Procaine

A

Local anesthetic

Na+ channel inhibitor

Blocks AP firing, (why you don’t feel pain)

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46
Q

Lidocaine

A

Local anesthetic

Na+ channel inhibitor

Blocks AP firing, (why you don’t feel pain)

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47
Q

3 Factors that determine size of single-channel currents

A
  1. Permeability
    (determined by ion and channel - do they “like” each other?)
  2. Ion concentration
  3. Membrane voltage
    (higher v = more ions can pass through)
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48
Q

Single channel conductance equation

A

i = γ(Vm-Vrev)

γ = single-channel conductance
Vm = membrane potential
Vrev = reversal potential
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49
Q

Whole cell current determined by 4 factors

A
  1. Total # of channels on PM
  2. Single-channel conductance (γ)
  3. Single channel Po
  4. Electrochemical driving force
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50
Q

Clamp info

A

Add!

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51
Q

Reversal potential

A

Potential at which there is no net flow of currents

52
Q

Open probability vs. open time

A

Open time: usually set threshold at 50% of amp; measure that as open time; numerical mean

Open prob: make open time histogram –> use distribution to find open time, do same thing for close time

53
Q

Single-channel open probability

A

Sum(open times)

/total recording time

54
Q

How is K+ channel so selective?

Puzzling sincle Na+ is smaller

A

Different water shells

Takes more energy to strip water away from Na+ than K+ (dehydration energy higher in Na ions)- this bc Na moles are smaller, ∴ water moles are able to exert stronger weight

When enter selectivity filter, surrounded by AAs that form surrogate hydration (no energy cost to ion due to physical-chemical arrangement of s.f.); matches arrangement

55
Q

K+ entering process

A

When K+ ions approach, getting into pore, loses 4 H2O replaced by AA

Normal arrangement: 4 above, 4 below

56
Q

Current-voltage relationship

A

Current grows bigger w/depolarization

57
Q

Subunit movement

A

Formed by S6 segment + s.f.

S4 moves in response to depolarization
S4 movement pulls on S4/S5 linker
S4/S5 linker causes change in S5/S6, that will open/close pore

58
Q

Capsaicin

A

chili pepper, spicy molecule

59
Q

TRPV1

A

Cation channel, R for capsaicin

Important for temp

Can have lower gate and s.f. - the 2 can open/close independently

60
Q

Channels can have…

A

1 or 2 gates
At different locations
And s.f. can act as gate

61
Q

Ligand-gate relationship

A

Ligand binding site is far away from gate

Causes wave of conformational change

62
Q

Functions of ion transporters

A
  1. Create/maintain ion gradient

2. Uptake NTs

63
Q

Ion channels vs. ion transporters

A
  1. Transporters need ATP, channels don’t
  2. Transporters are slower
  3. Transporters move at least ion ion Against conc.gradient, channels only conduct down
64
Q

Ion channel vs. transporter relationship

A

Channels are essential for setting up RMP
If open…dissipation of ion [ ] gradient
–> ∴ need TRANSPORTERS to restore gradient

65
Q

2 types of ion transporters

A
  1. Ion pumps (ATPases)
    Na/K pump, Ca pump, H pump
  2. Ion exchangers
    Antiporters, cotransporters
66
Q

Ion pumps mechanism

A

Use ATP hydrolysis energy to transport ions

Na/K: High Na out, high K in

67
Q

Ion exchangers mechanism

A

Indirectly use ATP, use gradients to drive ions in/out

(1) Antiporters - ions go against conc.gradient in diff directions
(2) Cotransporters - ions go in same direction
68
Q

Ion exchangers mechanism

A

Indirectly use ATP, use gradients to drive ions in/out

(1) Antiporters - ions go in different directions
(2) Cotransporters - ions go in same direction
69
Q

Na/Ca transporter

A

[Antiporter]

Na transported in…

Exchanger uses this energy…

….to take Ca out

70
Q

Na/H transporter

A

Only occurs when inside of cell becomes acidified (bc usually pH similar on both sides)

Na in…

Exchanger uses this energy to take

…H out

71
Q

Ion transporter properties

A
  1. (Some) ions transported against conc.gradient
  2. Requires ATP, either directly or indirectly
  3. Some ion transporters are ELECTROGENIC (mem pot. can be affected by electrical activity)
72
Q

Jens Sken

A

Discovered Na/K pump

73
Q

Na/K pump - discovery and importance

A

Originally discovered by Jens Sken

Without Na/K pump - no RMP, to AP, no LIFE

74
Q

Na/K pump is electrogenic

A

Meaning…

75
Q

Oubain

A

Poison made in adrenal glands, also found in plants
Drug used to treat certain types of heart failure (↑↑ pumping)

Experimental effects…

76
Q

Palytoxin

A

Can bind where oubain binds and makes pump permanently active

Which ions?

77
Q

Physiological role of Ca pump

A

Keep intracellular [Ca2+] low

or restore concentration (working overtime)

78
Q

How do ions eventually cause voltage/signaling?

A

Ion movement produces current
Current changes voltage
Membrane voltage used for signalling

79
Q

3 types of transient voltage changes

A
  1. Receptor potential (produced by external sensory stimuli, mainly in specialized sensory organs)
  2. Synaptic potential (produced at synapses)
  3. AP

RP and SP are usually local voltage changes, usually passive propagation/summation

80
Q

Where are signals produced in neuron

A

Local signals produced in dendrites/soma

Axon hillock = trigger zone

Traveling from soma to hillock = passive propogation

81
Q

Transient electrical signals - 3 important characteristics

A
  1. Magnitude
  2. Time course (kinetics)
  3. Propagation (depends on distance and speed)
82
Q

Passive propagation is determined by…

A

Membrane properties of neuron

83
Q

Current equation

A

I = V/R

Current = voltage/resistance

84
Q

Current-voltage relationship

A

Linear

85
Q

What factors determine magnitude of voltage?

A

ΔVss = I * Rin

I we control, Rin = input resistance of cell

  • Conductance
  • Size (bigger cell = bigger membrane = more channels = higher conductance = lower resistance)
  • Higher open prob = lower resistance
  1. Channel density
  2. Single-channel conductance
  3. Size of cell
  4. Open probability
86
Q

Conductance formula

A

g = 1/R

Conductance is the inverse of resistance

87
Q

Specific membrane resistance (Rm)

A

Size-independent
Resistance of a given area of membrane

Factors:

  1. Po
  2. # of channels
  3. PM conductance/resistance
88
Q

Capacitance take-home

A

Cell mem is a capacitor

2 conducting plates w/insulator in between

The larger the capacitance, the more charges you can store

If PM was just a conductor, membrane-voltage-Δ would be instantaneous; instead it is delayed

89
Q

Dialectic constant

A

Water has high DC (80)

Oil has low (2)

90
Q

How does size affect capacitance?

A

Magnitude and time course greatly affect AP firing

  • larger capacitance = slower the response = timing/frequency would decrease
  • smaller capacitance = can be charged more quickly = faster response = timing/frequency would increase
91
Q

What determines passive conduction?

A
  1. # of leak channels on membrane(if current very leaky most of the current you inject will leak out)
  2. Diameter
    (how much current can go through; charges bumping each other quickly)
  3. Resistance of cytoplasm
    (higher resistance=more likely current is to x)

Bigger SA, more channels, more leaking

  1. Resistance/conductance of PM
92
Q

Conduction of sea animal vs. mammalian axon

A

Squid giant axon

Sea squid cyto should be MORE conductive

  • Sea animal cyto has very high salt; high salt = more conductive
  • Larger diam - so rho (resistance) for squid axon is very low

SEE NOTES

93
Q

Rho/ϱ

A

Resistance of 1cm^3 of cyto

Constant

94
Q

Passive membrane propogation

A

Propagates passively without activating voltage channels, ∴ subthreshold

Factors:

  • Membrane input resistance
  • Capacitance (slows down mem voltage)
  • Time course

Distance depends on

  • Mem properties
  • Size of processes (dendrites, axons)
  • Intrinsic properties
95
Q

First ones to record APs

A

Alan Hodgkin
Andrew Huxley

Used electrodes to record APs on squid axon

Able to completely describe biological phenomenon through math

96
Q

What can we learn from single-channel recordings?

A

We can see single-channel conductance

- Plot amplitude of currents against voltage to get i-V relationship

97
Q

4 Patch Clamp Configurations

A
  1. Cell-attached
  2. Whole-cell
  3. Inside-out
  4. Outside-out
98
Q

Cell-attached patch clamp

A

1.

99
Q

Whole-cell patch clamp

A

2.

100
Q

Inside-out patch clamp

A

3.

101
Q

Outside-in patch clamp

A

4.

102
Q

What is reversal potential?

A

Potential at which there is no net flow of ions across membrane

Refers to the fact that a change of membrane potential on either side of the equilibrium potential reverses the overall direction of ion flux

103
Q

Electrogenic

A

Producing a change in the electrical potential of a cell

104
Q

Electrogenic

A

Producing a change in the electrical potential of a cell

105
Q

How is Na/K+ activity affected by extracellular [K+]?

A

-

106
Q

Train of axons

A

-

107
Q

How is ouabain used as a heart medication?

A

Increases heart pumping

Inhibits Na/K+ pump, [Na] inside cardiac cell ↑slightly

The ↑[Na] will inhibit the Na/Ca exchanger (antiporter), making it go slower; ∴ less Ca pumping out

↑ in Ca inside makes muscle contractions stronger

108
Q

Na/K+ pump

A

3 Na out, 2K in

109
Q

Ouabain effect on AP

A

Blocks Na/K+ pump

If pump is blocked with ouabain, AP will burst sooner and faster

110
Q

Input resistance

A

Rin= Vss / i

Reflects the extent to which membrane channels are open.

A low resistance (high conductance) implies many open channels, while high resistance implies many closed channels

111
Q

Tau

A

Time constant

A quantitative measure of how fast the membrane responds to current flow

Make sure you know how to do this

τ = Rin * C

112
Q

Change in voltage over time

A

ΔV(t) = ΔVss (1-e^(-t/τ)

113
Q

Factors for AP conduction velocity

A

Conduction velocity is directly proportional to nerve fiber diameter and degree of myelination

(The larger the diameter of the nerve the lower the resistance there is to the flow of current along its length)

The larger the fiber type diameter and the more abundant the myelin, the faster the nerve conduction velocity.

114
Q

λ

A

Lambda/length constant

Mathematical constant used to quantify the distance that a graded electric potential will travel along a neuron via PASSIVE electrical conduction

The greater the value of the length constant, the farther the potential will travel

115
Q

Po response to voltage

A

Po increases with depolarization –> reaches max level (~80%)

Overall: voltage-dependent parabola

116
Q

Conductance response to voltage

A

Conductance increases further and further w/depolarization because more and more channels opening faster and faster

117
Q

Feedback Cycle

A

Diagram in notes

118
Q

AP trajectory and diagram

A

In notes

119
Q

K+ equilibrium potential

A

-80 mV

120
Q

Na+ equilibrium potential

A

+60 mV

121
Q

Driving force

A

When an ion is not at its electrochemical equilibrium, an electrochemical driving force (VDF) acts on the ion, causing the net movement of the ion across the membrane down its own electrochemical gradient

Vdf = Vm − Veq

Push to reach equilibrium

122
Q

What does RMP reflect in regard to ion equilibrium potentials?

In general, what determines where it settles?

A

RMP is -60, which is closer to Ek than Ena - this is because there are many K+ leak channels on PM and few Na

Thus the membrane is many more times permeable to K+

In general, depends on:

  • # of channels
  • open probabilities
123
Q

Refractory periods

A

x

124
Q

3 factors that affect AP conduction speed

A
  1. Myelination
  2. Axon diameter (more diam = lower resis)
  3. Extracellular K+
125
Q

Myelin made by…

A

Macroglia

Schwann cells in PNS

Oligos in CNS
(single oligo can wrap around many cells)

Neurobiology (6 decks)

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