4. Neurophysiology I Flashcards
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
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
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
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
Ex
Lidocaine
• Lidocaine reduces pain by blocking ____ channels in the nerves
• Why does this matter?
sodium
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
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
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
Action potentials
• Amplitude ____ – all or none, >____ mV
• ____ spread to neighboring membrane
• Amplitude ____ with distance from initial site
Active propagation perpetuates
constant
50
active
constant
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
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+
____ changes in the permeability to Na+ and K+ underlie the action potentia
time-dependent
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
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 ____»_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
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
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+
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+
Gating of ion channels: how do they open and close
• Changes in voltage can gate the membrane > \_\_\_\_ changes in voltage sensitive ion channels
allosteric
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
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
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
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 \_\_\_\_
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
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
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
