Action Potential

So you are interested in Learning "Neurophysiology" well nice decision

Everything related to nervous system depend on Neurons their behaviour , their response and their character and let me just mention that Neurons are among one of the super special cells which are excitable ... (other being the muscle cells and glomus cells ) and we all know that they are excitable and basically they get excited and then the information is sent to another neuron than to another and at last to the higher centre of brain and basically thats how everything works right well this seems so so simple to say but when we go at the molecular level it is not that simple

So we will be learning about the action potential to its micro detail I will be covering every detail of it like graded potential, fluctuation, refractory period, summation and propagation of potential across the neuron , So it will be a long journey but trust me it is an essential step to get into the world of neurophysiology , in short if you have an excellent idea of the molecular events in action potential than it will be a kid work for you to explain neuron fatigue , plasticity , reverberate pathway which students generally memorise as they are unable to understand it conceptwise .

(I SPEAKED SO MUCH JUST TO MOTIVATE YOU THAT DO NOT TO MISS THIS ARTICLE AS STUDENT USUALLY IGNORE THIS TOPIC They say --AHH.. action potential is crap it has no importance in exams.. BUT IT IS SUPER IMPORTANT FOR A PROPER UNDERSTANDING OF BIG CONCEPT )

So it will be a long journey to have a complete understanding of action potential , time to time i will update my article , as i do not want you to get bored or take this long topic as a burden.

Before starting and getting into action potential details i would like to polish up your super basic concepts that you will require during your whole medical journey , let's just learn everything relevant about "CHANNELS"

Caution :- below content is highly modified by me to make it simple and a little funny you are not supposed to write these wordings in exams this is just a simpler explanation for understanding

what are channels ?

Ever heared about ZEE-TV , SONY-SAB OK! OK! not a serial/drama fan , ever Heared of Aaj tak . you should have heared of them (i suppose) they are channel in your television media thay had nothing to do with the Physiology

In physiology A channel refers to a Protein Complex( not always protein ) which give a path to certain ion to move it either outside the cell or inside the cell

So basically imagine just like in a corridor there are different doors which leads to different room imagine the path from corridor to the room through the door as a channel

So a cell membrane contains a lot of channel of different types and for different ions to serve the purpose of exchange of those ions let's learn about these channels .

Type of channels

So to make things pretty simple and straightforward i will be classifying them by my way (do not write this in exam )

So we divide channels in two subtypes - gated or ungated

So before getting into detail of these let me tell you which criteria i had used to classify them i had basically used the criterion whether they are gated or not .. or in simpler language does these pathway (channel) have any door to them or not ..

let's understand it in a simple way consider you are entering in a room and actually from the door frame the door is missing so as there is no door it means you can freely move in and out of room as there is no one to stop you and that's the same case with the UNGATED channel --- In short they are "NOT GATED" they do not have have obstruction means to whatever ions these channels are specialised it can freely move through them based on its concentration gradient

look at the image below to get more clear understanding :-

let's stick to ungated channel and discuss about them some interesting things

so as you can see any ions can move freely through these channels so they are also popularly known as - "Leaky channels" yeah ! you might have heared about leaky  K ⁺ channels and leaky sodium channels through which these ions are continously moving in and out based upon their concentration gradient

Leaky channels are basically the Ungated channels ...

So i think you must be clear why through leaky channels ions can move freely based on their concentration gradient

Now let's have a talk on Gated channels :

So Gated channels .. Imagine the same condition you are entering in a room and you are the ion but this time on door frame there is a door and that is closed with lock so basically to enter in that room you need to open the door and for that you require a key to open the door

you get the key open the lock and then the door and then enter into the room , Basically the gated channels are just like this condition . in Gated channels (Door frame with door) the protein complex has a obstruction (closed door) which require a stimulus(key) to allow the passage of that specific ion

see the diagram below for a clear understanding :-

so long story short - Gated channels are guarded and they require some stimulus to overcome this gate and to go to their destined location

now what is that stimulus? which they require .... and it is that stimulus which defines what type of gated channel they are .

Ever heared of

• Ligand gated channel
• Voltage gated channel
• Mechanical stimulation gated channel
• Thermal gated channel

you must have heared about them let me clear you

In "LIGAND GATED CHANNEL" it is the ligand which is actually the stimulus (key) which open up the gate that has obstructed the path in gated channels , it means whenever that ligand get available these channel get opened and ions start moving across its concentration gradient --Ever heared that nicotinic receptor actually open up the ligand gated cation channels for depolarization , in that case Acetylcholine is actually that ligand .

In " VOLTAGE GATED CHANNEL" it is the voltage fluctuation which opens up the gate and allow ion influx or efflux -- ever heared of voltage gated sodium channel !

In " MECHANICAL AND THERMAL GATED CHANNEL " it is actually the mechanical pressure and thermal fluctuation which trigger the opening of gate of these type gated channels --- they had a lot of importance in ascending tracts and are found abundantly in neuron contributing to merkel disc .

So i think you must be clear now about these channels because the whole neurophysiology basics lie on behaviour of these channels

Fast recap:-

Ungated channels are "leaky channels" ions are basically free to move in and out based on their concentration gradient

Gated channel have a gate whose opening and closing decides whether there will be a movement across them or not and their opening and closing depend on a particular stimulus it can be via a Ligand , thermal, mechano or even voltage can be a stimulus

However there is a lot more to talk like difference between Voltage gated sodium and potassium channel but i will be covering them witht the concept when there will be a requirement .

Structure of a Neuronal membrane

so lets understand how these channel are actually present in neuronal membrane

Observe the above given diagram very carefully and follow the text given below:-

1)- shows you - Voltage gated potassium channel

2)- shows you - Voltage gated sodium channels

3)- shows you- Mechanically gated channels

4)- shows you - Leaky or ungated Potassium channels

5)- shows you- Leaky or ungated sodium channels

6)- Sodium Potassium pump.

again, I want you to look the diagram very carefully and understand , how the ions channels are arranged on neuronal membrane

OK! Let's move forward now:-

Now before moving further i want you to tell some basic things again .

SEE- we call Cells as bag of potassium because potassium is present more on inner side of cells (in cytoplasm) but the sodium is more on the outer side ( extracellular fluid)

NOTE DOWN again--

INTRACELLULAR Conc. of potassium >> EXTRACELLULAR Conc. of potassium

INTRACELLULAR Conc. of sodium << EXTRACELLULAR Conc. of sodium

For a reference inside neuron INTRACELLULAR potassium = 140mM and EXTRACELLULAR potassium = 5mM(millimolar)

so that means there exist a concentration gradient for both the potassium and sodium across the neuronal membrane.

let's have a look what happens to potassium

so as there is more potassium on inner side of cell than outer side so , there will be a natural tendency of the potassium to move outside along its concentration gradient to maintain equilibrium so Potassium start moving from inner side of cell to external side via Ungated potassium channels and this process must go on until equilibrium is attained

Let's have a look what this process actually does to the potential of neuron

As potassium start its efflux its concentration start decreasing inside the cell due to this negative charge dominates on inner side of cell (particularly due to chloride ion ) potassium is actually present as potassium chloride which gets disassociated inside the cell in potassium cations and chloride ions , but due to regular efflux of potassium cations , charge inside the membrane become negative and more negative with time as chloride ions are still inside of neuronal membrane as there are no leaky chloride channels

look at diagram below to understand what i just said above -

so Scientist used Nerst equation to find out the Equilibrium potential of potassium ..

wait!! let me tell you what is an Equilibrium potential ? so imagine Equilibrium is achieved by potassium ions so that would have generated a negative charge on inner side of neuronal membrane so basically that potential is actually what we call as the Equilibrium potential (Frankly speaking it would take an another article specially on Equilibrium potential to really explain what it is you just need to have an idea of its role )

Still do not understand it ? Let's take an another simpler way of explanation

Equilibrium potential refers to that extra negative potential that we need to apply so that it would have prevented the potassium from its efflux

so in real life potassium ion do efflux and there arises a negative potential on inner side and Researcher used the Nernst equation to basically found out that potential (equilibrium potential )

Note- Potential is a relative term Researcher had assumed the reference of outer side potential as 0.

and the value that come out after applying Nernst equation was = -84mv

So Equilibrium potential of potassium = -84mv

Membrane is in resting stage as it is not excited so this must be the Resting Membrane Potential

So ideally speaking Equilibrium potential of Potassium must be = Resting membrane potential BUT.... that does not happen .....:( Because conditions are not ideal . let me tell you why ?

Why Equilibrium Potential of Potassium is not equal to RMP?

Actually the nerst equation gives us the value when full equilibrium is achieved but in real condition inside neurons it is never achieved .. Wanna know why?

Actually the whole surface of neuronal membrane is not permeable to potassium , potassium can just go out via leaky potassium channel which are limited and due to that limitation equilibrium would take a very very long time to achieve so in real life at resting stage it's potential is actually less negative than -84mv and it is -70mv and that is what we call as Resting membrane potential

Imagine yourself that now less potassium is going outside due to limitation of number of leaky potassium ions so compared to that ideal equilibrium condition more potassium are actually stuck inside which neutralises the internal negative charges causing a less negative potential to develop as compared to Equilibrium potential of potassium and that is what we call as the "Resting membrane Potential "

Note- there is also a very minute contribution from leaky sodium channel in causing less negative equilibrium potential as Sodium influx via those channel also neutralises the inner negative charges

Look at the graph below :-

so i think you might now be clear with the concept of Resting membrane potential and Potassium Equilibrium potential and why they are not equal and why the RMP is negative .

Threshold Potential

Now it's time to talk about threshold potential and it is an very interesting thing to understand . We will be talking out this a lot but at the moment to simplify things i want you to understand that , it is that potential value at which the Voltage gated sodium and potassium channel get activated

look as we know the RMP= -70 mv and let me tell you that the Voltage gated channel require -55 mv potential to get activated and when that is achieved we will see an increased electrical activity and a propagating current wave in neuron itself that we call as ACTION POTENTIAL

So note carefully RMP=-70mv and threshold potential for action potential is = -55mv . NOTICED SOMETHING...--- Threshold potential is actually less negative than RMP it means that we need more positive charge on inner side and as positive charge accumulate more and more on inner side the potential become less negative and less negative and may achieve threshold potential

How we will get that extra positive charge inside the cell ? that's a million dollar question. well let's find out the answer .

as i already told you that there are more sodium cation on outer side of the cell , what if somehow we bring those sodium inside the cell , if they come inside the cell than the potential of cell will become less negative ( because + charge has entered ) and it may achieve the threshold value .

How we gonna get those sodium cations inside the cell ???

ok before finding out the answer , let's look at the graph now :-

Graded potential .

ok so we are on the question - How we gonna get those sodium cations inside the cell ?

Did you remember i told you something about the gated channel and i told you about different types like - Mechanically gated channel , thermal gated channels , vibration gated channel , Ligand gated channel .

well let me tell you there are channels on the membrane called as Ligand gated sodium channels, mechanically gated sodium channels and thermally gated sodium channel

Depending on the situation neuron membrane contains one of them in abundance Like if you are talking about the touch receptors - merkel disc which detects the superficial pressure than in nerve ending supplying to those disc has a lot of mechanically gated sodium channel , if you talk about nerve ending sensitive for thermal changes than they contain a lot of thermally gated sodium channel and if you talk about pain receptors than there nerve endings has a lot of Ligand (bradykinin,histamine,substance P, prostagalndins) gated sodium channels

Let's understand their importance - so to get a crystal clear understanding we gonna take a example of neuron which is sensitive to touch

So if the nerve ending is sensitive to touch than it means it contains a lot of Mechanically gated sodium channels now what happens when you touch that area of skin which is supplied by those touch sensitive nerve endings ?

Let's find out -

so basically when you touch the area of skin which is supplied by those touch sensitive nerve endings than it opens up the gate of mechanically gated sodium channel and once there gate is open sodium start influx (as it is more on outer side) and as sodium start accumulating inside the potential become less and less negative from -70mv(RMP) ---> -65mv--> -60mv but suppose that it does not achieve the threshold value because the touch to that area was so lenient that you did not feel anything

I want your attention now , BE ATTENTIVE .

i said that you touched the area of the skin but it was very lenient that you did not felt anything means there was no action potential generated in that neuron because the stimulus (touch) you provided was less than the threshold value but as you touched there has been activation of some mechanically gated sodium channel and some sodium for a limited amount of time did entered inside of cell and even decreased the potential but it never touched the threshold but there was some fluctuation in the potential and we call that local , non propagating potential as - Graded Potential

see the image below :-

See in the above image , Gate of Mechanically gated sodium channel get open on touch and influx of sodium starts and and if that touch was able enough to open enough Mechanically gated sodium channel that it can cause an enough decrease to RMP that it achieves the threshold value we will feel the touch sensation and we can say that that the stimulus was of threshold intensity but if you touched the skin but did not feel it it means that touch (mechanical stimulus ) has opened mechanically gated sodium channel and there was a influx of sodium ions and the RMP has become less negative but it did not achieved the threshold value and we call that LOCAL (within a neuron) potential fluctuation as - Local potential or Graded potential .

look at the graph below :-

see the above graph.

Point A- you touched but did not feel any sensation although potential has decreased to less negative value but did not achieved the threshold value suppose the potential fluctuation was -70mv(RMP)---> -67mv

Point B- you again touched with a more intensity but again did not feel any sensation although potential has decreased this time to a more less negative value but did not achieved the threshold value suppose the potential fluctuation this time was -70mv(RMP) --> -62mv

Point C- you again touched with a more intensity but again did not feel any sensation although potential has decreased this time to a more less negative value but did not achieved the threshold value suppose the potential fluctuation this time was -70mv(RMP) --> -58mv

as we can see there can be several value of this local potential until it does not achieve the threshold and start propagating across the neuron network it is a local potential that has many value that's why it is called as "GRADED"{has many grades(level)} and that's why we say that Graded potential is actually an local potential or non propagating potential .

NOTE- graded potential can be hyperpolarizing (we will talk about this later)

Note - Just as we learnt the example of touch sensitive nerve endings same things happens in thermal sensitive nerve endings but there occurs via thermal gated sodium channel and in synapse same thing happen via ligand gated sodium channel

Thanks for reading , stay updated, I will be updating my article time to time and further content will be available

--signing off

Bhavesh saini ;)