4. Neurophysiology I Flashcards

1
Q

Small Changes in Ko have big impact on EK

Increasing Ko by 4.5 mM depolarizes EK by ____ mV

Decreasing Ki by 10 mM depolarizes EK by ____ mV

Increasing Nai by 14 mM hyperpolarizes ENa by ____ mV

Decreasing Nao by 22 mM hyperpolarizes ENa by ____ mV

It’s all in the ratio
of ____ to ____ concentrations

A

19
3
18
4

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2
Q

Adding only 4.5 mM K+ to the extracellular solution depolarized the membrane by ____ mV

Removing 22 mM Na from the extracellular solution hyperpolarized the membrane by ____ mV

Increasing the permeability of Na to = K depolarized the membrane by ____ mV

This increase in ____ puts the “Action” in action potential

A

8.1
2.4
62
PNa

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3
Q

Take home messages from homework

  • Changes in ____ have a big impact on EK and on Vm because Ko usually low and because relative permeability high.
  • Increases in the relative permeability of the membrane to ____ have a big impact on Vm because ENa very depolarized

The greater the ____, the more influence an ion has on the membrane potential

A

Ko
Na+
permeability

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4
Q

So, we know

1) there is a electrical potential where ions at a given concentration are in balance (____)
2) the more permeable a membrane is to a particular ion X, the closer the membrane potential gets to ____

How do electrochemical gradients and changing permeability signal along a nerve membrane?

A

Nernst potential, Ex

Ex

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5
Q

Lidocaine
• Lidocaine reduces pain by blocking ____ channels in the nerves
• Why does this matter?

A

sodium

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6
Q

The membrane potential can be measured using electrodes

* Traditionally used with electrodes, connected to  \_\_\_\_, measure difference in potential from ref electrode to inside cell
* Electrode filled with  \_\_\_\_,  \_\_\_\_ to move
* And translate solutional signal into  \_\_\_\_ signal with  \_\_\_\_ electrode > measure changes in membrane potential
A
volt-meter
potassium chloride
free
electrical
silver chloride
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7
Q

Optical measurements of membrane potential enable location information

Action potential signals from axons and dendrites loaded with membrane- potential sensitive ____ - great for studying neurons where ____ signal across regions

* Voltage sensitive dyes > advantage: can look at changes in membrane potential in diff parts of \_\_\_\_ (dendrites, soma, axon, etc.)
* \_\_\_\_ of signal > sub 3 mV changes are weak, but the \_\_\_\_ information is astounding
A

styryl
heterogeneous
neurons

accuracy
spatial

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8
Q

Graded potentials
• Amplitude ∝ ____, few mV to 10 mV
• ____ electrical spread to neighboring membrane
• Amplitude ____ with distance from initial site

____ diffusion of charge runs out

* \_\_\_\_ neurons - the larger you poke the arger the amplitude
* Further from intial site, the smaller the amplitude of the singal
A
stimuli strength
passive
decreases
passive
sensory
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9
Q

Action potentials
• Amplitude ____ – all or none, >____ mV
• ____ spread to neighboring membrane
• Amplitude ____ with distance from initial site

Active propagation perpetuates

A

constant
50
active
constant

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10
Q

The action potential -
all or none once reach threshold

* Rapid response, whole thing is over in \_\_\_\_ msec
* RMP > depolarization from adj parts of membrane > \_\_\_\_ (point of no return) > continue all the way, depolarize into the positive portion > \_\_\_\_, rapidly the repolarization begins > hyperpolarization > brief period, you are more negative than resting potential > \_\_\_\_, \_\_\_\_ period
A
1.5
threshold
overshoot
undershoot
refractory
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11
Q

Action potential 1: Membrane potential

  1. Resting potential very negative, close to EK: K+ ____ dominates
  2. Peak potential very positive and close to ENa: ____ permeability dominates
  3. Rapid repolarization: less
    influence from ____ as inactivation
    • Reduction in permeability to sodium, and increase with potassium
  4. Brief undershoot: relative permeability to ____ greater than at rest
A

permeability
Na+
PNa
K+

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12
Q

____ changes in the permeability to Na+ and K+ underlie the action potentia

A

time-dependent

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13
Q

The Action Potential 2: Changes in relative conductance

Looking at the changes in conductance over the course of action potential:
The conductance is a term that’s analog to ____ and is the inverse of ____.

The lower your resistance, the higher your ____ analogous to
your increased ____ to the ions.

This is a ____ scale on the y axis **

A

permeability
resistance

conductance
permeability

log

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14
Q

Action potential due to changes in relative permeability to K+ and Na+

  1. To begin with, (and at the end) the “resting” membrane potential, conductance to ____&raquo_space;Na+
  2. Na+ channels open as membrane ____ – voltage gated but as they open, membrane depolarizes further: ____ feedback-key to rapid
    depolarization. As long as depolarize past a given threshold voltage, this positive feedback continues all the way until the ____ of an action potential
    • Speed at which sodium permeability increase (speed at which channels open) is much greater
  3. K+ channels also
    open as membrane depolarizes but with ____ – slow rise and stop peak getting to ENa
  4. Na+ channels ____ with time – shut closed so
    influence of ENa is ____- lived.
    • Within few hundreths of a ms, Na channels inactivate
    • Domination of Na on potential is very rapid, very short
    • As Na inactivate, rise in ____ of K channels
  5. K+ channels shut more ____ as membrane gets more negative
    • As they open, they bring the potential to Ek - very negative
    • K are ____ dependent, but they’re slower to open, as the membrane becomes more negative, the ____ of K decreases, but slower
A

K+
depolarizes
positive
peak

delay

inactivate
short
permeability

slowly
voltage
conductance

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15
Q

Changes in conductance determine changes in membrane potential

Sodium channel activating and we go rapidly from
-90 to +10. We see the K+ channel conductance is
____ as the Na is ____. As we get
hyperpolarized, the K+ channels shut down. The
+10 mV is a much shorter period than the diagram
is showing but this is just another way to look at it

A

increasing

inactivating

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16
Q

Absolute and relative refractory periods

• Absolute refractory period – impossible to initiate another ____ because Na+ channel ____ or soon to be inactivated.

• Relative refractory period – ____ to initiate action potential because voltage- dependent ____ channels
open, pulling V
towards ____.

A

action potential
inactivated

harder
K+

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17
Q

Positive and negative feedback cycles in an action potential

  • Opening of Na+ channels lets Na+ enter cell, which ____ membrane and further opens ____ channels
  • Opening of K+ channels lets ____ exit cell, which hyperpolarizes membrane, decreasing the number of ____ channels that open
A

depolarizes
voltage-dependent Na+
K+
voltage-dependent K+

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18
Q

Gating of ion channels: how do they open and close

• Changes in voltage can gate the membrane > \_\_\_\_ changes in voltage sensitive ion channels
A

allosteric

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19
Q

Action potential due to changes in relative permeability to K+ and Na+

____ the membrane

____ channels open first, then inactivate ~1 msec

K channels open with ____, close when potential hyperpolarized

• A voltage sensor in both channels, a series of AA with \_\_\_\_ charges that can move easily through the channels
• Both start in closed configuration, when MP is depol, the more + on inside, the voltage sensor of Na, physically moves towards the \_\_\_\_ of the channel > opens up the Na channel (\_\_\_\_) > Na rapidly drives in (large electrochemical gradient)
• As soon as Na opens, inactivating \_\_\_\_ it snaps the channels shut again, Na+ has access to \_\_\_\_, but cannot access other side > inactivated state for as long as membrane is depolarized [voltage sensor is \_\_\_\_, but \_\_\_\_ is blocking from cytoplasmic side]
• When membrane is hyperpolarized, the \_\_\_\_ moves back tdown and \_\_\_\_ moves out the way, which is closed
	○ \_\_\_\_ GATES

• Do same with K, start with volt sensor closed when mem is hyperpolazied, then depol and voltage sensor takes \_\_\_\_ to move through
	○ At same time as \_\_\_\_ of Na
• K flow out of the channels, and hyperpolarizes the cell, unlike Na, they don't \_\_\_\_, as long as depolarize K will flow through, but when you hyperpolarize, the voltage sensor moves back down and closed
	○ \_\_\_\_ GATE
A

depolarize
Na
delay

positive
outside
allosterically

ball-and-chain
pore
open
ball-and-chain

voltage sensor
ball-and-chain
two

longer
inactivation

inactivate
one

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20
Q

Changes in conductance relate to physical changes in channels

When we talk about the ball
and chain: ____-
____-____

(IFM) is the inactivating ball
and is what moves to border the blocking once they have access when the Na+ channel opens.

A

isoleucine
phenylalanine
methionine

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21
Q

Changes in conductance relate to physical changes in channels

Resting membrane potential:
Voltage-sensor in ____ position, voltage gate ____
Inactivation gate open
No ____ flows

Depolarized membrane potential:
____ charges repel voltage- sensor, cause movement of segments resulting in opening of ____.
Inactivation gate still open.
____flows

Depolarized membrane potential:
____ still open.
____ gate closes.
No ____ flows

* Normally negative charges in side
* This is at rest Na channel
* Initial gate is closed > depol > positive charges casue voltage sensor (voltage dependent) (out of way > allosteric changes opens voltage gate > Na flows through quickly > the ball chain (time dependent) then goes into place
A

resting
closed
current

positive
voltage gate
current

voltage gate
time-dependent inactivation
current

22
Q

Action potential shape varies

  • Shape influenced by ____ of ion channels
  • Impacts function

In muscle, more neg because ____ helps prevent K run down ECl ____ mV

In ventricle, voltage-dependent ____ channels open on depolarization to prolong contraction

* Keep \_\_\_\_ more negative because you don't want contractions for a long time
* Cardiac > \_\_\_\_, prolong the contraction, in heart you want a long contraction to squeeze blood through
* Changing ions channels > changing in \_\_\_\_
A

distribution

Cl-
-93

Ca++

skeletal
Ca++
timing

23
Q

Ion channel pathologies mutations cause varied disorders

Long QT syndrome
• Usually mutations in \_\_\_\_ channels
• K+ channels reduced \_\_\_\_
• \_\_\_\_ weak, delayed
• Distorts \_\_\_\_, new AP kicks in before membrane repolarized
• \_\_\_\_ used
• Mutations that delay repolarization > depolarized for\_\_\_\_:
	○ Distorts rhythm > trying to start another \_\_\_\_ when depolarized
A

K+
conductance
repolarization
rhythm

EKG
repolarization
AP

24
Q

Long QT syndrome and the Dentist

* Common genetic issue where heart shows delayed \_\_\_\_
* Impt for dentists bc they're more likely to have sudden \_\_\_\_ attacks - avoid \_\_\_\_ that prplong QT syndrome, may need general anesthetic, don't want normal sense of \_\_\_\_ pushing them into arrest
A

repolarization
cardiac
drugs
adrenaline

25
Q

Primary ____ pain caused by Na+ channel mutation

  • Mutations in Na+ channel make it more ____
  • Channel expressed in ____ ganglion nerves responding to pain
  • Patients with mutation have intermittent ____ pain.

Remember, blocking ____ channels major target for analgesics like lidocaine

* More active Na+ > more liekly to get to \_\_\_\_ > larger current through sodium channels
* Blocking channels > target for lidocaine and other pain relievers
* \_\_\_\_ that make others more sensitive to pain than others
A

eryhermalgia
active
dorsal root
burning

Na+

threshold
polymorphisms

26
Q

A real action potential

Increased pressure depolarized membrane potential, opens ____ channels so initiate action potentials

* Changes in pressure > increase \_\_\_\_ > train of AP that hit threshold, remove pressure they go away
* Hit threhsold, depolarize quickly
A

Na+

pressure

27
Q

Action potentials
Summary:
1) Resting membrane potential is dominated by the resting ____
2) The rising phase of an AP is dominated by ↑ in ____
3) The falling phase of an AP is dominated by ↑ ____
4) The absolute refractory period is due to ____ of the PNa.

A

Pk
PNa
Pk
inactivation

28
Q

Functional anatomy of a neuron

____ are the synapses. ____ is the transmission through the axon.

A

output

throughput

29
Q

Axon Hillock-making action potential

  • Needed to convert ____ potential to ____ potential
  • Na+ sensitive dye shows more influx i.e. open ____ in hillock
  • Antibodies show more ____ channels in hillock
    • Record signals through neuron there are different ____ in axon hillock
    • Look at Na influx along length of axon during AP, theres a region where ____ levels are higher
    • Myelinated soma > little change; close to soma, small increase in sodium, further away only small icnrease in sodium, at the ____ > big increase of Na when AP goes through > corresponds to inc in number of voltage dependent sodium channels > in this region, so they are ready to respond and make AP when depolarization reaches them
A

graded
action
channels
Na+

conductances
sodium
axon-hillock

30
Q

Dendrites
• Receive signals
• Convey information to soma
• Dendritic spine structural ____
• Spine ____ and ____ related to strength of signal
• Spines ____: change based upon input, can increase with learning

* Increase surface area, increase interface to comm with incoming neurons, increasing \_\_\_\_ after period of learning
* Increase signalling between cells with right \_\_\_\_ frequency > spines increase
A
protrusion
shape
thickness
plastic
thickness
temporal
31
Q

Distribution of ion channels on dendritic spines changes with activity

____ channels determine amplitude and width of local dendritic spikes generated by ____ clustered and ____ synaptic input, and curtail dendritic Ca2+ signals generated by synaptic input or by back-propagating action potentials. These channels affect forms of plasticity that depend on back-propagating action potentials or the propagation of local dendritic spikes

Activity-dependent trafficking of
K+ channels.
1. KV4.2 channels and KCa2.2 channels are ____
2. Kir3.2 channels inserted in ____ PP1)
3. KV2.1 channels de-cluster upon ____ stimulation

* Distribution of K channels > during activation and LTP > an internalization of K channels > fewer of them, the \_\_\_\_ is not going to be as strong, and \_\_\_\_ will be enhanced > useful in LTP
* Controlling balance of sodium and K channels in membrane, you cn affect learning
* Can move ions into dendtritic spine in repsonse to these changes
A

K+
spatially
temporal

internalized
synapse
glutamate

repolarization
depolarization

32
Q

Axons – transmission and transport
• Transmit electrical signal
• Transport proteins, growth factors, waste to and from synapse
• Defects in transport lead to disease

* Getting things from nucleus to synapse - logistical nightmare > \_\_\_\_ that have problems transporting back and forth
* \_\_\_\_ rapid transport of vesicles
A

neural disease

bidirectional

33
Q

Defects in axonal transport associated with Alzheimer’s Disease

• ____ cannot transport mitochondria, other cargo to and from soma

* Beta amyloid and tau
* Tau - transport material along the axon - if they become phos, they can no longer transport material effectively
* Accumulation of waste
A

phosphorylated tau

34
Q

Roles of neuronal sections
• ____ – input, processing
• ____ – maintenance, processing
• ____ – output, processing ?

____ distributed to fit role

• Passive spread to soma, if depolar is sufficient to activate Na channels in \_\_\_\_ > coded into AP
A

dendrites
soma/hillock
axon

ion channels

axon-hillock

35
Q

Glia - key player in neuroscience

  • ____ – communicate between blood and neurons, can release transmitters into synaptic cleft
  • ____ – immune cells of nervous system
  • ____ - myelin
    • Active contribution to neural signaling and health
    • Astrocytes - ____ on vessels to receive nutrients, comm to neurons and synpase
    • Oligos - wrap signal, control ____
    • Microglia - can become too ____ and eat up neurons
A

astrocytes
microglia
oligodendrocytes

end-feet
transmission
aggressive

36
Q

Astrocytes support neurons
• Bridge between ____ and ____ – nutrition
• Control ionic concentration – maintain ____ levels!

* In \_\_\_\_, communicate all along the neuron
* Prevents depolarization of system by high etracell K+ levels
A

BV
neurons
extracellular K+

nodes of ranvier

37
Q

Astrocytes contribute to synaptic signaling

Three-way synapse (pre-synaptic, post-synaptic neurons, and astrocytes picking up ____ and
releasing ____ into
synaptic cleft).

Astrocytes can release a lot of neurotransmitters from their ____. Not just one way, there are ways in which
astrocytes can communicate
across whole system.

A

waste
compounds

lysosomes

38
Q

Microglial cell activation involves ____ system

• Atp, adeonosine, from astrocytes can attract \_\_\_\_ cells (P2YR), and activations tates where \_\_\_\_ are released
A

purinergic
microglial
pro-inflam cytokines

39
Q

Protection by microglial cells

* Usually phagocytose bits of \_\_\_\_, amyeloid beta
* Release \_\_\_\_, help the neurons prosper
* Lead to communication where \_\_\_\_ are recruited and differentiated
A

myelin
GF
SC

40
Q

Glial cells degrade amyloid beta

In a healthy brain extracellular A-beta degraded by ____ and ____ expressing Endothelin-Converting Enzyme (ECE), Neprilysin (NEP), and Matrix Metalloproteinases (MMPs). A-beta peptides are internalized through ____ and ____

* ECE bind Abeta
* LRP/SR-A1 internalize, and broken down in \_\_\_\_
A

microglia
astrocytes

low-density lipoprotein receptors (LRP)
scavenger receptor-A1 (SR-A1)

41
Q

Glial cells and inflammation in AD

During Alzheimer’s disease (AD), A-beta molecules accumulate as ____. In response, activated astrocytes, microglia, and macrophages release pro- inflammatory cytokines such as ____, ____, and ____. Starts as ____, ends as pathological

• \_\_\_\_ is apparent
A
plaques
TNFalpha
IL-1beta
IL-6
oxidative stress
42
Q

Depolarization moves along the membrane

Approaching depolarization moves voltage sensor, opens Na+ channels – ____ spread via cable properties

K+ channels open with ____, Na+ channels inactivate, action potential moves

____ flow of depolarizing current to adjacent areas of membrane

Opens voltage-gates Na+ channels – if reaches threshold then ____ feedback to AP
____ of Na+ channels keeps depolarization moving in one direction

• Channels that you leave behind are \_\_\_\_, \_\_\_\_ maintains \_\_\_\_ movement
A

passive
delay

passive

positive
inactivation

refract
relative refractory
unidirectional

43
Q

Passive current flow won’t get you far Active current flow gets you there slowly

Even ____ flow not good way to transmit across long distances:

Takes more time and current to change potential because of ____ of + and – charges

Low ____ across membrane –takes a lot of ____ to maintain gradients

A

active
proximity
resistance
energy

44
Q

Membrane is a leaky capacitor

Thinner membrane = ____ capacitor, ____ charge stored, ____ time to charge before membrane potential set

Thicker membrane = ____ capacitor, ____ charge stored, ____ to charge membrane

Remember electroneutrality – Charge difference concentrated at membrane, opposite charges attracted to each other

Leak channels dissipate gradient along axon Takes lots of ____

• Capacitor is a way of separating charges
• Leak channels - \_\_\_\_ pore channels - requires more energy
****• Increase \_\_\_\_, stop \_\_\_\_, and \_\_\_\_ capacitor
A

larger
more
longer

smaller
less
quicker

energy

two
resistance
leak
reduce

45
Q

Axons conduct electrical signals over long distance

Action potential must move from cell body along axon to synapse – must move a ____ quickly

A

long distance

46
Q

Speed of neuronal impulses

 • 0.1-100 m/s: cross body in msec
(in wires, current travel at 3x108 m/s.)
• Speed affected by
– \_\_\_\_ –temperature α speed
– \_\_\_\_ - diameter α speed.
– Marine invertebrates, have \_\_\_\_ axons to speed responses as sea water cold.
– Giant squid axon
(not axon of a giant squid)
* \_\_\_\_ environement - more rapidly signal transmited
* Larger \_\_\_\_ - more rapid the signal goes
* Giant axons of squid - larger diameter axons, swimming in cold water
A
temperature
axon diameter
thick
warmer
axons
47
Q

Speed of neuronal impulses

– Vertebrates, ____ sheath instead of large diameter
– sheath acts as insulation – increases ____, decreases ____
– voltage-gated ion channels only at the nodes of Ranvier so action potential jumps ~ ____ between nodes - ____.
– Increases speed from 1 m/s (unmylenated) to ____ m/s (mylenated).

• Speeds increase 100-fold - saves energy, do not have to maintain \_\_\_\_ to same extent, and \_\_\_\_ is greatly enhanced
A
myelin
resistance
capacitance
1mm
saltatory propagation
100

gradients
speed

48
Q

Passive current flow won’t get you far Active current flow gets you there slowly

• Requires more \_\_\_\_ to change membrane potenital
A

energy

49
Q

Myelin used to increase speed, stop loss of signal to transmit over distance

Charges further apart: decreases ____

Higher ____: current not lost

Myelin ____ resistance across membrane ____x ____ capacitance across membrane ____x

* Cover with myelin, no \_\_\_\_ in this area - the passive flow of Na goes quickly to next node > activates quickly and leads to AP
* Bigger effect of myelin is on \_\_\_\_
* In regions, you need to minimze myelin - optic nerve is \_\_\_\_, great for vision, but high \_\_\_\_ demand where you must maitain gradient - susceptible to damage (slower)
A

capacitance
resistance

increases
5000
decreases
50

leakage
resistance
unmyelinated
energy

50
Q

Myelin damaged in multiple sclerosis

Auto-immune destruction of ____, forms scars
Impedes neural ____

* Reduction in \_\_\_\_, and a demand for extra \_\_\_\_
* Slower transmission, bc cannot rely on \_\_\_\_
* \_\_\_\_ - first sign - test bc otrasnsmision of visual signal along optic nerve takes \_\_\_\_ bc myelinated portion that leaves eye breaks down - problems with vision
* Depends on whether affects other parts of body - difference bt \_\_\_\_ and \_\_\_\_
A

myelin
transmission

speed
energy
saltatory transmission
optic neuritis
longer
optic AID
MS
51
Q

Summary

During an action potential, depolarization opens voltage- dependent Na+ channels, Na+ enters and depolarizes the membrane further until the channels inactivate

Increasing ____ permeability repolarizes the membrane towards EK

Differential distribution of ____, or ____ in these channels, can alter the ____ of the action potential.

The neuron is composed of many dendrites, a soma, and one axon, with action potentials generated in the ____.

____ flow of depolarizing current along the axon allows transmission of the action potential.

The myelin sheath increases ____ across the axonal membrane to make transmission of action potential ____ and more successful over long distances

A

K+
channels
mutations
shape

hillock

passive

resistance
faster