Exam I Review Flashcards

(125 cards)

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
Why do cells need ion potentials?
- 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
26
Essential properties of ion channels
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)
27
Roderick MacKinnon
Nobel prize for chem in 2003 Found structure of ion channels worked with Kcsa K+ channel
28
Cryo-electronmicroscopy (Cryo-EM)
Historically low resolution, improved to high res in 2013 | Allowed for many channels to be discovered
29
What allowed for many ion channels to be discovered?
``` Roderick MacKinnon (first discovered ion channels) Cryo-EM ```
30
NDMA receptor
Important for learning and memory
31
Why are ion channel structures important?
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
32
Classification of ion channels
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) ```
33
Nonselective cation channels
Allow all POS ions to pass through Typically K+ and Na+, sometimes Ca2+
34
Gating
Opening/closing of channel Even LEAK CHANNELS can close All ion channels go between these 2 states
35
4 ways to open/close a channel
1. Voltage change (mostly opened by dep.) 2. Ligand binding/unbinding 3. Membrane stretch /mechanical force 4. Temperature change
36
Inactivated state
Many channels have this stage Allows AP to be unidirectional (refractory period) I cannot be opened by stimulus
37
Tetrodotoxin
TTX Puffer fish toxin Na+ channel inhibitor
38
Saxitoxin
STX Shellfish toxin Na+ channel inhibitor
39
Tetraethylammonium
TEA K+ channel inhibitor Often used in research
40
Ba2+
K+ channel inhibitor
41
Dihydropyridines
Ca2+ channel inhibitor
42
Cd2+
Heavy metal Ca2+ channel inhibitor Many heavy metals can block channels
43
Curare
Blocks nicotinic ACh receptor on NMJ
44
β-bungarotoxin
Snake toxin | Blocks ACh receptor
45
Procaine
Local anesthetic Na+ channel inhibitor Blocks AP firing, (why you don't feel pain)
46
Lidocaine
Local anesthetic Na+ channel inhibitor Blocks AP firing, (why you don't feel pain)
47
3 Factors that determine size of single-channel currents
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)
48
Single channel conductance equation
i = γ(Vm-Vrev) ``` γ = single-channel conductance Vm = membrane potential Vrev = reversal potential ```
49
Whole cell current determined by 4 factors
1. Total # of channels on PM 2. Single-channel conductance (γ) 3. Single channel Po 4. Electrochemical driving force
50
Clamp info
Add!
51
Reversal potential
Potential at which there is no net flow of currents
52
Open probability vs. open time
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
Single-channel open probability
Sum(open times) | /total recording time
54
How is K+ channel so selective? Puzzling sincle Na+ is smaller
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
K+ entering process
When K+ ions approach, getting into pore, loses 4 H2O replaced by AA Normal arrangement: 4 above, 4 below
56
Current-voltage relationship
Current grows bigger w/depolarization
57
Subunit movement
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
Capsaicin
chili pepper, spicy molecule
59
TRPV1
Cation channel, R for capsaicin Important for temp Can have lower gate and s.f. - the 2 can open/close independently
60
Channels can have...
1 or 2 gates At different locations And s.f. can act as gate
61
Ligand-gate relationship
Ligand binding site is far away from gate Causes wave of conformational change
62
Functions of ion transporters
1. Create/maintain ion gradient | 2. Uptake NTs
63
Ion channels vs. ion transporters
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
Ion channel vs. transporter relationship
Channels are essential for setting up RMP If open...dissipation of ion [ ] gradient --> ∴ need TRANSPORTERS to restore gradient
65
2 types of ion transporters
1. Ion pumps (ATPases) Na/K pump, Ca pump, H pump 2. Ion exchangers Antiporters, cotransporters
66
Ion pumps mechanism
Use ATP hydrolysis energy to transport ions Na/K: High Na out, high K in
67
Ion exchangers mechanism
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
Ion exchangers mechanism
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
Na/Ca transporter
[Antiporter] Na transported in... Exchanger uses this energy... ....to take Ca out
70
Na/H transporter
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
Ion transporter properties
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
Jens Sken
Discovered Na/K pump
73
Na/K pump - discovery and importance
Originally discovered by Jens Sken Without Na/K pump - no RMP, to AP, no LIFE
74
Na/K pump is electrogenic
Meaning...
75
Oubain
Poison made in adrenal glands, also found in plants Drug used to treat certain types of heart failure (↑↑ pumping) Experimental effects...
76
Palytoxin
Can bind where oubain binds and makes pump permanently active Which ions?
77
Physiological role of Ca pump
Keep intracellular [Ca2+] low | or restore concentration (working overtime)
78
How do ions eventually cause voltage/signaling?
Ion movement produces current Current changes voltage Membrane voltage used for signalling
79
3 types of transient voltage changes
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
Where are signals produced in neuron
Local signals produced in dendrites/soma Axon hillock = trigger zone Traveling from soma to hillock = passive propogation
81
Transient electrical signals - 3 important characteristics
1. Magnitude 2. Time course (kinetics) 3. Propagation (depends on distance and speed)
82
Passive propagation is determined by...
Membrane properties of neuron
83
Current equation
I = V/R Current = voltage/resistance
84
Current-voltage relationship
Linear
85
What factors determine magnitude of voltage?
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
Conductance formula
g = 1/R Conductance is the inverse of resistance
87
Specific membrane resistance (Rm)
Size-independent Resistance of a given area of membrane Factors: 1. Po 2. # of channels 3. PM conductance/resistance
88
Capacitance take-home
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
Dialectic constant
Water has high DC (80) | Oil has low (2)
90
How does size affect capacitance?
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
What determines passive conduction?
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 4. Resistance/conductance of PM
92
Conduction of sea animal vs. mammalian axon
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
Rho/ϱ
Resistance of 1cm^3 of cyto Constant
94
Passive membrane propogation
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
First ones to record APs
Alan Hodgkin Andrew Huxley Used electrodes to record APs on squid axon Able to completely describe biological phenomenon through math
96
What can we learn from single-channel recordings?
We can see single-channel conductance | - Plot amplitude of currents against voltage to get i-V relationship
97
4 Patch Clamp Configurations
1. Cell-attached 2. Whole-cell 3. Inside-out 4. Outside-out
98
Cell-attached patch clamp
1.
99
Whole-cell patch clamp
2.
100
Inside-out patch clamp
3.
101
Outside-in patch clamp
4.
102
What is reversal potential?
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
Electrogenic
Producing a change in the electrical potential of a cell
104
Electrogenic
Producing a change in the electrical potential of a cell
105
How is Na/K+ activity affected by extracellular [K+]?
-
106
Train of axons
-
107
How is ouabain used as a heart medication?
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
Na/K+ pump
3 Na out, 2K in
109
Ouabain effect on AP
Blocks Na/K+ pump If pump is blocked with ouabain, AP will burst sooner and faster
110
Input resistance
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
Tau
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
Change in voltage over time
ΔV(t) = ΔVss (1-e^(-t/τ)
113
Factors for AP conduction velocity
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
λ
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
Po response to voltage
Po increases with depolarization --> reaches max level (~80%) Overall: voltage-dependent parabola
116
Conductance response to voltage
Conductance increases further and further w/depolarization because more and more channels opening faster and faster
117
Feedback Cycle
Diagram in notes
118
AP trajectory and diagram
In notes
119
K+ equilibrium potential
-80 mV
120
Na+ equilibrium potential
+60 mV
121
Driving force
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
What does RMP reflect in regard to ion equilibrium potentials? In general, what determines where it settles?
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
Refractory periods
x
124
3 factors that affect AP conduction speed
1. Myelination 2. Axon diameter (more diam = lower resis) 3. Extracellular K+
125
Myelin made by...
Macroglia Schwann cells in PNS Oligos in CNS (single oligo can wrap around many cells)