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a barrier to outside of cell which is achieved by the____?

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ch 1-4

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1

a barrier to outside of cell which is achieved by the____?

cell membrane -> defines intra- vs. extra-cellular spaces

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2

cytosol?

aqueous solution (liquid) inside the cell

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3

cytoplasm?

everything between nucleus and plasma membrane (i.e. cytosol + organelles)

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4

phospholipid bilayer?

hydrophilic + hydrophobic

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5

hydrophilic?

interacts with water/environment; H2O lover, polar; phosphate head

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6

Hydrophobic?

interacts with water/environment; H2O lover, polar; lipid tail

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7

Cellular membrane?

Membrane plays a critical role in communication between cells 

Membrane is dynamic; protein components change and move around = critical for neuroadaptations

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8

cytoskeleton?

protein scaffold

  • localization and interconnection between organelles

  • gives shape to neurons or glia

  • dynamically modulated (it plays role in the plasticity of neurons)

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9

cytoskeleton parts?

Microtubule – conveyor belt

Intermediate filament – cell structure

Microfilament – membrane scaffold

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10

mitochondria?

Major site of ATP production, O2 utilization, and CO2 formation  - THE POWERHOUSE OF THE CELL!

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11

rough ER

Ribosomes synthesize proteins

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12

smooth ER

Stores enzymes to make lipids and steroids

Stores Ca++ for cellular processes

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13

golgi apparatus?

  • Concentrates, modifies, and sorts proteins arriving from RER

  • Packages proteins in vesicles

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14

nucleus?

contains the DNA

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15

nuclear envelope?

surrounds nucleus

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16

neurons?

cells that send and receive information in the form of chemical/electrical signals

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17

compartmentalization/functional segregation of neurons?

Dendrites = input

  • receive signal

Body = protein production

Initial Segment = integration (axon hillock)

  • where neuron decides to send signal or not

Axon = conduction/propagation

  • of AP of signal

Terminal = output

  • where neuron sends message

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18

Afferents?

  • go “to” CNS from PNS

  • sensory neurons

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19

Efferents?

  • efferents go “away from”; CNS to PNS

  • motor neurons

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20

Interneurons?

remain in the same area (don’t project anywhere; not afferent or efferent since don’t move

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21

neurotransmitters ex?

dopamine, norepinephrine, serotonin, GABA, glutamate, etc

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22

Excitatory neurotransmitters?

encourage a target cell to take action

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23

Inhibitory neurotransmitters

decrease chances of the target cell taking action

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24

Modulatory neurotransmitters

send messages to many neurons at the same time, or even communicate with other neurotransmitters

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25

glial?

provide structural support in nervous system, make myelin, immune (immune survalience) & neuronal functions (neurogenesis & apoptosis)

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26

Myelin?

protective fatty coating of axons to increase the speed at which they transmit messages

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27

myelin producing glia are?

1. Oligodendroglia (CNS)= Myelinates many axons

2. Schwann cells (PNS)= Only myelinates 1 axon

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28

ependymal cells?

Specialized cells that line the ventricular system of the brain and play a key role in the production of cerebrospinal fluid (CSF) in brain and spinal cord.

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atrocsytes

  • star-shaped cells

  • assist in the transfer of nutrients and waste

    • wrapped around blood vessels

    • also take up and release ions, thus making them important for neurotransmission

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30

atoms?

  • neutral particles

  •  # protons = # electrons

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31

not all atoms are stable?

  • atoms want to have 8 electrons in their outer shells to be stable. 

***2 electrons in outer shell if only one shell (hydrogen)

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cations (+)?

lose an electron they now have a positive charge

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33

anion (-)?

gain an electron they now have a negative charge

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34

“like attracts like”?

Polar molecules attract other polar molecules and repel non-polar molecules

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35

water dissolves polar molecules?

salt & sugar cuz polar

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36

hydrophilic dissolves?

polar and dissolve in water

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37

hydrophobic dissolves?

nonpolar and do not dissolve in water

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38

hydrophobic molecules can go through membrane?

yes go straight through (O2, CO2, N2)

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39

hydrophilic molecules can go straight through membrane?

no, blocked by lipid tails

  • ions: Cl-, K+, Na+

  • small uncharged polar molecules: H2O, ethanol

  • large uncharged polar molecules: glucose, sucrose

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40

intra vs extra cellular contents?

  1. there is a difference in the concentration of specific ions and proteins across the cell membrane 

  2. the cell membrane is selectively permeable to some of these ions

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41

compare ion concentrations intra & extra cellular?

intra: K+ & anion (-) high

  • neg banana

extra: Na+ & Cl- , Ca2+high

  • salty milk

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42

resting membrane potential (-65 or -70 mV)?

Relative net ionic differences between inside and outside of cell with outside defined at 0

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43

2 forces establishes membrane potential?

1) diffusion

2) electrical charge

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44

diffusion (force #1)?

the movement of molecules down a concentration gradient

requires:

  1. Concentration Gradient (H to L)

  2. The ability to move (channels)

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45

resting membrane potential is determined by?

resting membrane potential is determined by selective permeability AND the direction of the concentration gradient. 

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46

electrical charge (force #2)?

opposite charges attract and like charges repeles attract and like charges repel

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47

ohm’s law?

Current = Potential * Conductance

Current = flow of electrical charge

Potential = membrane potential

Conductance = resistance, existence of ion channels

(If potential increases, current flow increases; If resistance increases (e.g. fewer ion channels = less conductance), current flow decreases)

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48

how would you increase conductance of a neuron? What would happen to ionic current?

increase ion channels; more channels so more ions come through

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49

how would you increase potential of a neuron? What would happen to ionic current?

depolarize neuron; increases as Na+ comes into cell because of diffusion & electric charge force

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50

equilibrium potential?

diffusion & electrical potential is balanced out; ions still move=1 comes in as 1 leaves cell (no net movement)

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51

Nernst equation?

If the concentration difference across the membrane is known an equilibrium potential can be calculated for any ion.(only use for single ions)

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52

relative permeability?

The ability of an ion to cross the membrane can be expressed relative to the ability of all other ions.

  • ion that can cross more readily=high “relative permeability” to an ion that passes less readily

  • Flow of ion(s) with high relative permeability contribute more to the membrane potential; i.e. membrane potential will be close to the ion’s equilibrium potential.

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53

Goldman equation?

Relative permeability serves to weight the contribution of an individual ion to the membrane potential which is mathematically incorporated into the Goldman equation as Pion

  • use for multiple ions

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54

Channel?

passively allow ions to cross membrane; no ATP

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55

pump?

 actively (requires energy) move ions across membrane; needs ATP; major determinant in concentration gradients (ex: 3 Na+ out for every 2 K+)

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Co-Transporters and Exchangers?

use concentration gradient (H to L) of one molecule to move another molecule against concentration gradient (L to H)

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57

Three major  factors influence ion movement through channels?

  1. # channels: determined by gene expressions

  2. single channel current (phosphorylation: channel open more=more ions come through)

  3. probability of channel opening: intrinsic gating properties and modulation

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58

resting membrane potential summary?

  1. Membrane has a large relative permeability to K+ versus Na+

  2. Membrane is impermeable to bulk of intracellular proteins (net anionic charge)

  3. Na/K Pump is electrogenic : (3 Na+ out of cell and 2 K+ in)

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59

action potential?

wave of depolarizing current that flows down the axon to the terminals

-brief (1/1000 sec reversal of membrane potential)

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pre-synaptic?

neuron before the synapse (sending the message)

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61

synapse?

space between two neurons

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62

post-synaptic neuron?

neuron after the synapse (receiving the message)

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63

EPSP = excitatory post-synaptic potential?

  • slight depolarization in membrane (closer to threshold)

  • due to influx of positively charged ions (typically Na+)

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64

IPSP = inhibitory post-synaptic potential?

  • Slight hyperpolarization in membrane

  • due to influx of negatively charged ions (typically Cl-) or efflux of positively charged ions (K+)

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65

initial segment/axon hillock?

  • Ions from IPSP/EPSP diffuse along surface of the membrane

  • Ions (depolarization/hyperpolarization) waves reach axon hillock

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66

voltage-gated Na+ channels open based on?

Open/inactivate/close and reset based on membrane voltage

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67

why is the axon hillock the trigger zone for AP?

Large number of voltage-gated Na+ channels at the axon hillock make it a “trigger zone” for the beginning of an AP

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68

Any given neuron can receive information (i.e. PSPs) from thousands of synaptic inputs. What could make certain PSPs more likely to influence if the neuron fires an AP?

if Na+ came in closer to hillock; bigger channels size

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69

What could make certain PSPs more likely to influence if the neuron fires an AP?

  1. Their size (e.g. a lot of Na+ influx)

  2. Their distance from the axon hillock

  3. Their frequency

  4. All of the above

All of the above

  1. more Na+ come in

  2. closer to axon hillock

  3. cuz Na+ keeps building up

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70

typical action potential?

1) resting state

2) rising phase

3) overshoot

4) falling phase

5) undershoot/hyperpolarization

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71

1) resting state?

activation gats on Na+ & K+ channels are closed & the membranes resting potential is maintained

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2) rising phase

rapid depolarization of the membrane (+)

  1. vg Na+ channels open, vg K+ closed, Na+ comes in making inside more pos w/ respect to outside

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3) overshoot peak (+30mV)

reaching about 40mV this is the points at which the inside of the neuron is positive with respect to the outside

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4) falling phase

rapid repolariztion (becomes more neg)

  • vg Na+ inactivate block Na+, activation on most K+ channels open permitting K+ exit cell so cell inside becomes neg

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5) undershoot/hyperpolarization

the point at which the cell is more negative with respect to the outside than at resting phase. 

There is a gradual restoration of the resting potential following undershoot.

  • both gates of Na+ channels are closed but the activation gates on some K+ channels still open; as these gates close most K+ channels & inactivation gates open on Na+ channels=>resting

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76

Two types of voltage-gated ion channels mediate changes in membrane permeability during the AP?

  1. Inactivating Voltage-gated Na+ Channel

  2. Delayed (Rectifying) Voltage-gated K+ Channel

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vg Na+ channels

  • closed but can opening at rest

  • open at threshold to peak potential (-50mV to +30mV); Na+ rapidly comes in

  • closed & inactivated (can’t open) from peak to resting potential (+30mV to =70mV) ; ball & chain blocks opening

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vg potassium channels

  • closed: @ resting potential delayed opening until threshold closed until peak potential (-70mV to +30mV);

  • open: from peak potential until hyperpolarization (+30mV to -80mV)

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79

ion channels at rest

  • non-gated K+ open: permeable to K+ cuz always open

  • vg Na+ closed

  • vg K+ closed

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80

ions channels at rising stage

  • non-gated K+ open: permeable to K+ cuz always open

  • vg Na+ open: cuz rapid depolarization (+)

  • vg K+ triggered

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81

ions channels at falling stage

  • non-gated K+ open: permeable to K+ cuz always open

  • vg Na+ channels inactivated

  • vg K+ channels closed

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82

ion channels at resting stage

  • non-gated K+ open: permeable to K+ cuz always open

  • vg Na+ channels reset/closed

  • vg K+ channels closed

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83

What do you think would happen if we use a drug to block the activity of voltage-gated Na+ channels?

  1. There would be no action potentials

  2. There would be more action potentials

  3. Nothing would happen

  4. All of the above

  1. There would be no action potentials; need Na+ vg channels to open in rising stage & depolarize (+)

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84

Tetrodotoxin (TTX) from pufferfish affects which ion?

Blockade of vg-Na+ channels = blockade of APs

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85

all or none?

need to reach threshold at axon hillock then fire AP; if not then no AP

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86

how does increase generator potential impact AP frequency?

input more EPSP increased frequency (#) of AP NOT THE SIZE

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87

absolute refractory period?

Neuron CANNOT fire another action potential at this time cuz…

  • Vg-Na+ channels are already open (-55mV to +30mV) OR (rising phase)

  • Vg-Na+ channels are inactivated +30mV to -65mV (peak to falling stage)

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88

relative refractory period?

Vg-Na+ channels are reset

Neuron is hyperpolarized! (K+ leaks out cuz vg K+ channels don’t close until -80mV)

Neuron can fire another action potential at this time, but it takes more EPSPs since -80mV is more neg than resting potential (-65mV)

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89

Why can AP only go in 1 direction?

in a absolute refractory period the vg Na+ channels are inactivated for the rest of the AP

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90

what impacts conductance speed?

  1. diameter

  2. insulation

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91

diameter larger vs smaller in conductance speed?

Larger diameter is faster (less axial resistance) less resistance agsnt ion movement

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92

what if Na+ leak?

As Na+ ions enter the axon they diffuse randomly down their concentration gradient => If ions “leak” (through pumps/channels/exchangers) from the axon, then it will take longer for a depolarization wave to reach the next vg-Na+ channels

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93

insulation in conductance speed?

Myelin serves to insulate axon:

reduces leakage - stronger repulsion down axon - faster conduction (saltatory conduction)

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94

myelination?

 speeds up electrical signal (creates greater membrane resistance)

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95

Saltatory conduction:?

“jumping” of electrical signal from node to node

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96

voltage-clamp electrophysiology?

  • Electrode to measure membrane potential (i.e. voltage)

  • This is the voltage clamp amplifier. It considers the membrane potential and injects current to achieve a specified membrane (i.e. voltage)

  • Measuring current flowing across the membrane 

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97

Using Voltage Clamp to Hyperpolarize the membrane exp1

-Inject current to hyper polarize the membrane – moving the membrane to -130mv

Measure current flow in and out of membrane. 

  • Initial capacitive current 

    • during voltage step only 

    • due to rapid change in voltage of the membrane

  • Then nothing. No ion movement across the membrane.

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98

why does using Voltage Clamp to Hyperpolarize the membrane results make sense? exp1

  •  voltage-gated Na+ channels don’t open for Na+ to pass into cell until threshold (i.e. -55mV)

  • voltage-gated K+ channels don’t fully open until the membrane is depolarized

So, at anything less then -55mV, there is no notable passage of ions across the membrane (just some leaking K+ channels and the Na+/K+ pump)

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99

Using Voltage Clamp to Depolarize the membrane? exp1

from -65 mV(resting) to 0 mV

Measure current flow in and out of membrane. 

  • Initial capacitive current 

    • during voltage step only 

    • Then immediate fast inward current (Na+)

    • Followed by a delayed lasting outward current

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100

why does Using Voltage Clamp to Depolarize the membrane results make sense? exp 1

  • depolarization of the membrane opens Na+ channels and Na+ floods into the cell

  • This is followed by the opening of voltage-gated K+ channels and K+ flowing out of the cell

  • Voltage-gated K+ channels are highly heterogenous – having different voltage-regulated and temporal dynamics. 

  • This experiment shows an inward followed by outward ion movement that is voltage dependent (relies on depolarization).

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