Tricky Topics: Action Potentials

Summary

This script explores how neurons communicate via electrochemical signals, focusing on action potentials. It explains the roles of excitatory and inhibitory postsynaptic potentials in reaching the threshold for an action potential. The video details the process of action potential generation, propagation along the axon, and termination at the axon terminals. It also touches on how substances like novocaine and tetrodotoxin can block sodium channels, affecting action potentials, and how drugs can manipulate neurotransmitter levels to treat conditions like depression and Alzheimer's.

Takeaways

• 🧠 Neurons communicate using electrochemical signals, with neurotransmitters playing a key role in transmitting messages across synapses.
• 🔋 Neurons have two main functions: transmitting messages to a target neuron via a synapse and carrying messages along the axon to the next neuron.
• 📈 Graded potentials, both excitatory (EPSPs) and inhibitory (IPSPs), determine when a neuron reaches the threshold to initiate an action potential.
• ⚡ Action potentials are electrical signals generated when the membrane potential reaches a threshold of -55 millivolts, leading to the opening of voltage-gated sodium channels.
• 🚀 Action potentials propagate along the axon to the terminals, with the nervous system operating within a sensitive computational timeframe, some traveling at speeds up to 100 meters per second.
• 🛡 Myelin sheaths, formed by glial cells, insulate axons and allow electrical charge to jump between nodes of Ranvier, increasing the speed of action potential propagation.
• 🔄 The action potential involves a cycle of depolarization, caused by sodium influx, and repolarization, caused by potassium efflux, to restore the resting membrane potential.
• 💊 Local anesthetics like novocaine block sodium channels, preventing the depolarization phase of action potentials, which is essential for nerve signaling.
• 🐡 Tetrodotoxin, found in pufferfish, is a potent sodium channel blocker that can be lethal by paralyzing the respiratory system.
• 🔗 When an action potential reaches the axon terminal, it triggers the opening of voltage-dependent calcium channels, which are necessary for neurotransmitter release through exocytosis.
• 🔄 Neurotransmitter release is terminated by either reuptake into the presynaptic neuron or enzymatic degradation in the synaptic cleft.

Q & A

How do neurons communicate with each other?

Neurons communicate with each other using the language of electrochemistry, primarily through the release of neurotransmitters and the generation of action potentials.

What are the two important jobs of a neuron?

A neuron's two important jobs are to transmit a message to a target across a synapse and to carry a message along the length of the axon to the next neuron.

What are the two types of postsynaptic potentials?

The two types of postsynaptic potentials are excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs).

What is the threshold membrane potential that triggers an action potential?

The threshold membrane potential that triggers an action potential is minus 55 millivolts.

How does the action potential propagate along the axon?

The action potential propagates along the axon through the sequential opening of voltage-gated sodium channels, which allows sodium ions to rush into the neuron, further depolarizing the membrane.

What is the role of myelin sheaths in the nervous system?

Myelin sheaths, formed by glial cells, insulate the axons and allow electrical charge to quickly jump between myelin segments, increasing the speed of action potential propagation.

What are nodes of Ranvier and why are they significant?

Nodes of Ranvier are the spaces between myelin sheaths that are densely clustered with ion channels, allowing the passage of electrical charge across the membrane and facilitating the rapid propagation of action potentials.

What happens when the membrane potential reaches positive 40 millivolts during an action potential?

When the membrane potential reaches positive 40 millivolts, voltage-gated sodium channels inactivate, and voltage-gated potassium channels open, leading to potassium efflux and the repolarization phase of the action potential.

What is the refractory period and why is it important?

The refractory period is a brief period of time when the neuron is hyperpolarized and unlikely to fire off another action potential, ensuring that the action potential only travels in one direction.

How do neurons terminate their response after an action potential?

Neurons terminate their response through two main methods: presynaptic reuptake, which uses transporter proteins to repackage neurotransmitters, and enzymatic degradation, which breaks down neurotransmitters in the synapse.

How do drugs like novocaine work to block action potentials?

Drugs like novocaine are sodium channel blockers, which prevent the depolarizing phase of action potentials, thus blocking the initiation of action potentials and causing a numbing effect.

What is tetrodotoxin and how does it affect the nervous system?

Tetrodotoxin is a powerful sodium channel blocker found in pufferfish. It can lead to paralysis and death by blocking action potentials in the respiratory system.

Outlines

00:00

🧠 Neuronal Communication and Action Potentials

This paragraph explains the fundamental aspects of neuronal communication, emphasizing the role of neurotransmitters in transmitting messages across synapses and the importance of action potentials for signal transmission along the axon. It details how neurons sum excitatory and inhibitory postsynaptic potentials to determine when to initiate an action potential, which is triggered when the membrane potential reaches a threshold of -55 millivolts. The paragraph also discusses the initial step of an action potential, which involves the opening of voltage-gated sodium channels, and how these channels are distributed along the axon. The movement of sodium ions into the neuron and the subsequent depolarization are described, along with the role of myelin sheaths in increasing the speed of action potentials.

05:02

🚀 The Propagation of Action Potentials

This section delves into the process of how action potentials propagate along the axon towards the neuron's terminals. It explains the role of voltage-gated sodium channels in initiating the action potential and how the influx of sodium ions leads to further depolarization. The paragraph describes the sequential opening of sodium channels along the axon, allowing the depolarization wave to travel towards the terminals. It also discusses the repolarization phase, where voltage-gated potassium channels open, leading to potassium efflux and the return of the membrane potential to its resting state. The refractory period, during which the neuron is temporarily unable to generate another action potential, is also explained.

10:04

🔄 The Cycle of Action Potentials

This paragraph focuses on the cycle of action potentials, starting with the resting membrane potential of a neuron and the threshold for initiating an action potential. It describes the depolarization phase, where sodium influx leads to a positive membrane potential, and the subsequent repolarization phase, where potassium efflux returns the membrane potential to its resting state. The refractory period is also mentioned, ensuring unidirectional propagation of the action potential. The paragraph concludes with a discussion of how neurons restore ion concentrations after an action potential and the role of graded potentials in initiating action potentials.

15:06

🌐 Termination of Neuronal Responses

This section discusses the termination of neuronal responses, which is crucial for the proper functioning of the nervous system. It explains two primary methods of terminating neural transmission: presynaptic reuptake and enzymatic degradation. Presynaptic reuptake involves transporter proteins that回收neurotransmitters into the presynaptic terminal for reuse, while enzymatic degradation involves the metabolic breakdown of neurotransmitters, rendering them inactive. The paragraph provides examples of drugs that affect these processes, such as SSRIs that block serotonin reuptake to treat depression and Alzheimer's drugs that inhibit the breakdown of acetylcholine to enhance memory signals.

Keywords

💡Neurons

Neurons are the fundamental units of the nervous system, responsible for transmitting information through electrical and chemical signals. In the video, neurons are described as having two main jobs: transmitting messages across a synapse via neurotransmitters and carrying messages along the length of the axon to the next neuron. This dual role is central to the video's theme of explaining how information is transmitted in the nervous system.

💡Action Potentials

Action potentials are electrical signals that transmit information along the length of a neuron's axon. The video explains that action potentials are generated when the membrane potential reaches a threshold of minus 55 millivolts, leading to the opening of voltage-gated sodium channels. This concept is crucial to understanding how neurons communicate over long distances.

💡Voltage-gated Sodium Channels

These channels are integral to the initiation of an action potential. As detailed in the script, when the neuron's membrane potential reaches a certain threshold, these sodium channels open, allowing sodium ions to rush into the neuron and causing further depolarization. This process is a key mechanism in the propagation of action potentials along the axon.

💡Neurotransmitters

Neurotransmitters are chemicals released from the presynaptic neuron that trigger graded potentials in the postsynaptic neuron. They play a critical role in the first job of neurons, which is to transmit messages across a synapse. The video distinguishes between excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials, which together determine when an action potential is initiated.

💡Graded Potentials

Graded potentials are local changes in membrane potential that can be either excitatory or inhibitory. They are the result of neurotransmitter binding to receptors in the postsynaptic neuron. The video explains how the neuron sums up all EPSPs and IPSPs to decide when to generate an action potential, which is essential for the neuron's second job of message transmission.

💡Myelin Sheaths

Myelin sheaths are fatty layers that insulate the axons of many neurons, allowing for faster conduction of action potentials. The video describes how these sheaths, formed by glial cells like oligodendrocytes, increase the speed at which action potentials travel, which is vital for the rapid communication within the nervous system.

💡Nodes of Ranvier

Nodes of Ranvier are the gaps in the myelin sheaths where ion channels are concentrated, allowing for the rapid transmission of electrical signals along the axon. The video uses these nodes to illustrate how action potentials can 'jump' from one node to the next, a process known as saltatory conduction, which increases the speed of signal transmission.

💡Depolarization

Depolarization refers to the process where the inside of the neuron's membrane potential becomes less negative, moving towards a positive value. In the context of the video, depolarization is initiated by the opening of voltage-gated sodium channels and is a critical phase in the generation and propagation of action potentials.

💡Repolarization

Repolarization is the process by which the neuron's membrane potential returns to its resting state after an action potential. The video explains that this occurs as voltage-gated potassium channels open, allowing potassium ions to leave the neuron and restore the membrane potential to a negative value.

💡Refractory Period

The refractory period is a brief interval following an action potential during which the neuron is unable to generate another action potential. As described in the video, this period of hyperpolarization ensures that action potentials only travel in one direction and that the neuron's response is controlled and precise.

💡Exocytosis

Exocytosis is the process by which neurotransmitters are released from the presynaptic neuron into the synaptic cleft. The video mentions that when an action potential reaches the axon terminal, it triggers the opening of voltage-dependent calcium channels, which are necessary for the exocytosis of neurotransmitters, completing the cycle of neuronal communication.

Highlights

Neurons communicate using electrochemical signals.

Action potentials are crucial for transmitting information over long distances.

Neurotransmitters trigger graded potentials in the postsynaptic neuron.

Graded potentials are either excitatory or inhibitory.

Action potentials are generated when membrane potential reaches threshold.

The axon's main job is to propagate action potentials to the neuron's target.

Voltage-gated sodium channels play a key role in the initiation of action potentials.

Myelin sheaths increase the speed of action potential propagation.

Nodes of Ranvier are areas of high ion channel concentration for electrical charge passage.

Action potentials propagate in a proximal to distal direction along the axon.

Sodium influx through voltage-gated channels is essential for action potential propagation.

Voltage-gated potassium channels contribute to the repolarization phase of action potentials.

The refractory period ensures unidirectional action potential travel.

Special pumps restore ion concentrations after an action potential.

Graded potentials vary in size, unlike action potentials which are all-or-none.

The strength of an action potential is coded by frequency.

Local anesthetics like novocaine block sodium channels to prevent action potentials.

Tetrodotoxin, a poison in pufferfish, is a powerful sodium channel blocker.

When an action potential reaches the axon terminal, it triggers calcium channels for neurotransmitter release.

Neurons terminate responses by reuptake or enzymatic degradation of neurotransmitters.

SSRIs work by blocking serotonin reuptake to treat depression.

Drugs like donepezil boost acetylcholine levels to improve memory in Alzheimer's patients.

Transcripts

[Music]

neurons communicate with each other

using the language of electrochemistry

and to appreciate how information is

transmitted across large distances in

some cases over a meter it's necessary

to understand how action potentials work

but first let's review the basics of

neuronal communication neurons have two

important jobs one is to transmit a

message to a target across a synapse and

the other is to carry a message along

the length of the axon to the next

neuron the first job is made possible by

neurotransmitters released from the

presynaptic neuron they trigger graded

potentials in the postsynaptic neuron

which come in two flavors excitatory

postsynaptic potentials or epsps and

inhibitory postsynaptic potentials or

ipsps the neuron has the ongoing task of

adding up all the epsps

and ipsps to determine when to start the

neuron second job of carrying the

message down the length of its axon if

the membrane potential reaches its

threshold of minus 55 millivolts a type

of electrical signal called an action

potential is generated the action

potential then triggers neurotransmitter

release once it reaches the terminals

and the process starts all over again in

the new neuron

although an action potential is first

generated where the membrane potential

reaches minus 55 millivolts which is

usually in the axon initial segment

right at the soma we'll focus on the

events in the axon since their main job

is to propagate the action potentials to

the neurons target at the terminals the

first step of an action potential is

opening of voltage-gated sodium channels

as a postsynaptic neuron receives

neurotransmitter signals if the

threshold of minus 55 millivolts is

reached a special type of sodium channel

that sensitive to electrical changes

gets opened let's take a quick look at

how different receptor types distribute

in a neuron

unlike the receptor channels in the

synapse that are neurotransmitter gated

that is they open in response to

specific neurotransmitter binding

voltage dependence sodium channels which

are most densely located in the axon

open when the membrane potential is

depolarized to minus 55 millivolts in a

resting neuron there are more sodium

ions outside the neuron than inside so

there's a chemical and electrical

imbalance that promotes sodium movement

inside the cell

thus when voltage dependent sodium

channels open sodium rushes into the

neuron bringing its positive charge

making the sell even more depolarized

once an action potential is initiated it

propagates along the axon to its

terminals if we think about the nervous

system as a whole

hundreds of millions of action

potentials are being fired on top of one

another at all times

thus the nervous system must operate

within a remarkably sensitive

computational timeframe indeed some

action potentials can travel at speeds

of up to a hundred meters per second one

strategy the nervous system uses to

increase action potential speed to as

quick as possible is the surrounding of

axon shafts with the fatty membranes of

glia cells

in the central nervous system

oligodendrocytes form fatty myelin

sheaths along axons as seen here this

insulates the axon allowing electrical

charge to quickly jump between myelin

within the axon the space between the

myelin sheaths are referred to as nodes

of ranvier if we zoom in into a node of

ranvier we see that this area is densely

clustered with ion channels which allow

the passage of electrical charge in the

form of ions across the membrane in

areas not covered by the myelin let's

now take a closer look at the mechanisms

behind an action potentials travel down

the axon away from the soma to the axon

terminals here we can see a neuron with

its axon extending away from its soma if

we take a cross-section along the length

of its axon and zoom in we can start to

appreciate what's happening inside the

neurons axon when the graded potentials

at the synapse add up to minus 55

millivolts this is detected by the

voltage dependent sodium channels which

are found in large numbers along the

axon as the voltage-gated sodium

channels open sodium rushes into the

axon along its electrochemical gradient

bringing its positive charge into the

neuron this depolarization is then

sensed by neighboring sodium channels

which also open when the membrane

potential reaches minus 55 millivolts

having sodium ions and positive charged

rush into the neighboring region of the

axial

at this time point if we were to stick

an electrode into the neuron we would

see the membrane potential rise at the

location where the sodium channels are

opening at this time point this location

is proximal to the soma that is it is

closer to the soma than the terminals

the wave of depolarization makes its way

down the axon as neighboring sodium

channels along each part of the axon

open allowing sodium to continue to flow

in

this depolarization wave travels in a

proximal to the stalled direction at a

time point - if we were to again stick

an electrode into the neuron the

depolarization would be measured farther

down the axon this process of sodium

channels bringing positive charge which

then opens adjacent voltage dependent

sodium channels works its way

uninterrupted

all the way down the length of the axon

so once an action potential gets started

it doesn't stop until it runs out of

neuron

while voltage-gated sodium influx is a

key mechanism of action potential

propagation it is only half the story

let's return to where we started at the

beginning of the axon in review when the

neuron is depolarized to minus 55

millivolts from graded potentials

voltage-gated sodium channels open this

allows sodium to travel across its

electrochemical gradient from outside

the neuron to inside the neuron this

causes a further depolarization of the

neuron to positive 40 millivolts when

the membrane potential reaches positive

40 millivolts two things happen one

voltage dependent sodium channels

inactivate and two voltage dependent

potassium channels open keep in mind

that potassium is more concentrated

inside the neuron so when its channel

opens its concentration difference is a

driving force for potassium movement

outside the neuron at a membrane

potential of positive 40 millivolts

there is also an electrical reason for

potassium to leave the neuron when

positively charged potassium leaves the

neuron it brings its positive charge

outside the neuron with it which makes

the membrane potential inside more

negative and helps to balance the charge

difference of the sodium influx let's

come back to the electrical voltage

recording of the axon at time point 1 if

we zoom in we can notice there are two

main components of the action potential

first when the cell reaches minus 55

millivolts it triggers an exponential

rise in the membrane potential to

positive 40 millivolts this rise is a

product of sodium influx through

voltage-gated sodium channels

once the action potential reaches

positive 40 millivolts its second

component can be seen the membrane

potential falls back to its negative

resting membrane potential this is due

to the closing of voltage-gated sodium

channels and more importantly the

opening of voltage-gated potassium

channels which allow the potassium

efflux out of the neuron this is the

repolarizing phase of the action

potential so if we come back to watch

our action potential travel down the

axon at each step along the axon

voltage-gated sodium channels open

followed by voltage-gated potassium

channels

understanding the voltage changes across

the membrane as the action potential

moves down the axon is essential to

understanding its propagation mechanisms

so let's again review the changes across

the membrane during an action potential

except one step closer at rest when the

neuron is not receiving any input its

membrane potential is at about minus 70

millivolts all the voltage-gated sodium

and voltage-gated potassium channels are

closed such that very few sodium ions

and very few potassium ions are moving

across the membrane if the neuron gets

enough excitatory postsynaptic

potentials and not too many inhibitory

postsynaptic potentials it will reach

the threshold of minus 55 millivolts and

the voltage dependent sodium channels

will open allowing for sodium influx

this is called the depolarization phase

which is the part of the action

potential where the membrane potential

climbs all the way to positive 40

millivolts a positive 40 millivolts the

sodium channels deactivate and the

voltage dependent potassium channels

open potassium leaves the neuron along

its electrochemical gradient taking its

positive charge with it this is called

the repolarization phase since the

membrane potential returns back to minus

70 millivolts for a brief period of time

potassium keeps moving out of the cell

hyperpolarizing the neuron so it sits at

less than minus 70 millivolts which

ensures that this segment of the axon

will be unlikely to fire off another

action potential this is called the

refractory period and ensures that the

action potential only travels in one

direction

finally once the action potential is

finished at a certain region of the axon

the neuron uses special pumps to restore

the ions to their regional

concentrations and only then is that

segment of the axon ready to fire again

let's put this all together by

considering a snapshot that captures all

the voltage changes over the duration of

an action potential from beginning to

end keep in mind that this is happening

all over the neuron but we're just

looking at one small segment of the axon

first let's focus in on graded

potentials which lead to action

potential initiation

however unlike action potentials which

are all or none graded potentials vary

in size as shown here graded potentials

can lead to different sizes of

depolarization or hyperpolarization x'

in contrast action potentials happen the

same way every time they're triggered so

the strength of an action potential is

coded by frequency or the number of

action potentials per time period a

strong signal will produce more action

potentials than a weaker one over the

same period of time our knowledge of how

ions work to generate action potentials

has allowed us to manipulate the process

to our advantage let's focus on the

depolarizing phase which is strongly

dependent on voltage dependence sodium

channels when the sodium channels open

sodium rushes into the cell kicking off

the whole process so what happens if

these channels are blocked so you need

to have dental work done that requires

drilling not a pleasant experience for

most people most dentists give an

injection of a drug like novocaine the

dead-end sensations in the mouth indeed

most local anesthetics used in dentistry

are sodium channel blockers which means

they prevent the depolarizing phase so

an action potential can't happen

an interesting fact is that drugs like

novocaine were originally derived from

cocaine which is one of the only few

naturally-occurring local anesthetics

part of the cocaine molecule acts as a

sodium channel blocker so it produces a

numbing feeling if rubbed on the gums by

modifying the cocaine molecule

scientists were able to keep the sodium

channel blocker activity but remove the

parts of the molecule that promoted

addictive behavior

how about this cartoon fish what does it

have to do with action potentials this

is the pufferfish which contains a

poison called tetrodotoxin concentrated

in certain organs like the ovaries and

the liver pufferfish can kill you lots

of ways if threatened by a predator they

may puff up which is how it got its name

you can actually die from eating certain

body parts of the puffer fish that

contain tetrodotoxin tetrodotoxin is a

powerful sodium channel blocker and even

tiny amounts can lead to paralysis and

death by blocking action potentials in

the respiratory system so far we have

discussed how an action potential is

initiated and then how it propagates

down the axon however what we haven't

discussed yet is what happens when an

action potential reaches the axon

terminal once an action potential

arrives at the terminal the depolarizing

wave opens up another type of channel

the voltage-dependent calcium channel

like sodium calcium is more concentrated

outside the neuron driving its movement

inside the neuron calcium is necessary

for neurotransmitter release through a

process called exocytosis where the pre

synaptic vesicle fuses with the terminal

membrane to release its contents into

the synapse now it's important that

neurons are responding in a

time-dependent manner so that their

activity is connected to the tasks we're

trying to accomplish for example if I

were to tell you right now to think of

your first-ever teacher you probably

didn't activate that memory until I

asked you to at some point before the

end of this video you'll probably stop

thinking about your first teacher so

your memory neurons turn on and off when

they are needed just as it is important

to initiate a neurons response it's as

important for neurons to terminate that

response when the job is done

there are two main methods to terminate

a neuronal response and they both

involve removing excess

neurotransmitters from the synaptic

cleft

the first way neurons terminate neural

transmission is by presynaptic reuptake

which uses specialized transporter

proteins that span the presynaptic

terminal membrane these transporters

relocate the neurotransmitter molecules

so that they can be repackaged into

synaptic vesicles and used again at a

later time drugs like SSRIs used to

treat depression work by blocking the

reuptake transporters for the

neurotransmitter serotonin allowing it

to hang around in the synapse for a

little longer low serotonin has been

implicated in depression symptoms so by

elevating its levels in the synapse

these drugs attempt to treat the

disorder

the second way neurons terminate neural

transmission is by enzymatic degradation

enzymatic degradation is the metabolic

breakdown of neurotransmitters in the

synapse you can think of it as the

neurotransmitters essentially being

eaten up so they no longer have

biological activity a great drug example

that takes advantage of enzymatic

degradation in the synapse is the

Alzheimer's drug den episode this drug

blocks the breakdown of the

neurotransmitter acetylcholine which is

reduced in the brains of Alzheimer's

patients this allows it to hang around

in the synapse longer and boost memory

signals that decline with the disease

taken together the action potential is

perhaps the most quintessential process

of the nervous system it is responsible

for transporting signals around the

nervous system and remarkably fast times

amazingly humans as well as other

animals like the pufferfish have figured

out ways to alter aspects of the action

potential hijacking the signaling of our

nervous system

[Music]

you

[Music]