4. Neurophysiology I Flashcards by J L

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

19
3
18
4

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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

8.1
2.4
62
PNa

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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

Ko
Na+
permeability

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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?

Nernst potential, Ex

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

sodium

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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

volt-meter
potassium chloride
free
electrical
silver chloride

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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

styryl
heterogeneous
neurons

accuracy
spatial

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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

stimuli strength
passive
decreases
passive
sensory

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

Active propagation perpetuates

constant
50
active
constant

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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

1.5
threshold
overshoot
undershoot
refractory

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Action potential 1: Membrane potential

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

permeability
Na+
PNa
K+

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

time-dependent

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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 **

permeability
resistance

conductance
permeability

log

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

To begin with, (and at the end) the “resting” membrane potential, conductance to ____&raquo_space;Na+
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
K+ channels also
open as membrane depolarizes but with ____ – slow rise and stop peak getting to ENa
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
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

K+
depolarizes
positive
peak

delay

inactivate
short
permeability

slowly
voltage
conductance

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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

increasing

inactivating

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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 ____.

action potential
inactivated

harder
K+

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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

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

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Gating of ion channels: how do they open and close

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

allosteric

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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

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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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.

isoleucine
phenylalanine
methionine

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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

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resting
closed
current

positive
voltage gate
current

voltage gate
time-dependent inactivation
current

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 \_\_\_\_

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distribution

Cl-
-93

Ca++

skeletal
Ca++
timing

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

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K+
conductance
repolarization
rhythm

EKG
repolarization
AP

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

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repolarization
cardiac
drugs
adrenaline

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

eryhermalgia active dorsal root burning Na+ threshold polymorphisms

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

Na+ | pressure

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.

Pk PNa Pk inactivation

Functional anatomy of a neuron ____ are the synapses. ____ is the transmission through the axon.

output | throughput

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

graded action channels Na+ conductances sodium axon-hillock

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

``` protrusion shape thickness plastic thickness temporal ```

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

K+ spatially temporal internalized synapse glutamate repolarization depolarization

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

neural disease | bidirectional

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

phosphorylated tau

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

dendrites soma/hillock axon ion channels axon-hillock

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

astrocytes microglia oligodendrocytes end-feet transmission aggressive

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

BV neurons extracellular K+ nodes of ranvier

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.

waste compounds lysosomes

Microglial cell activation involves ____ system • Atp, adeonosine, from astrocytes can attract ____ cells (P2YR), and activations tates where ____ are released

purinergic microglial pro-inflam cytokines

Protection by microglial cells * Usually phagocytose bits of ____, amyeloid beta * Release ____, help the neurons prosper * Lead to communication where ____ are recruited and differentiated

myelin GF SC

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 ____

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

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

``` plaques TNFalpha IL-1beta IL-6 oxidative stress ```

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

passive delay passive positive inactivation refract relative refractory unidirectional

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

active proximity resistance energy

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

larger more longer smaller less quicker energy two resistance leak reduce

Axons conduct electrical signals over long distance Action potential must move from cell body along axon to synapse – must move a ____ quickly

long distance

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

``` temperature axon diameter thick warmer axons ```

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

``` myelin resistance capacitance 1mm saltatory propagation 100 ``` gradients speed

Passive current flow won’t get you far Active current flow gets you there slowly • Requires more ____ to change membrane potenital

energy

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)

capacitance resistance increases 5000 decreases 50 leakage resistance unmyelinated energy

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 ____

myelin transmission ``` speed energy saltatory transmission optic neuritis longer optic AID MS ```

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

K+ channels mutations shape hillock passive resistance faster

4. Neurophysiology I Flashcards

(51 cards)