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Voltage gated potassium channels | Activation Cycle of Voltage Gated Potassium Channels

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This video will answer the following questions.

In this video we’ll talk about voltage-gated potassium channels as the name suggests the conductivity of these channel is dependent on the voltage change and these channels would conduct potassium when there is a change in voltage in this video we’ll learn the structure of voltage-gated potassium channel we learn the gating kinetics we’ll also focus on the function

And the classification of voltage-gated potassium channel so stay tuned till the end of this video this is a overview to the uh potassium channel structure we can see this is the n terminal this is a c terminal and inside the membrane we can see there are several transmembrane alpha helices which which contains the voltage sensor domain the fourth helix is

Actually the voltage sensor helix this has a lot of positively charged residue which is responsible for this voltage sensing mechanism in between fifth and the sixth helix there is a p loop which harbors the selectivity filter the selectivity filter ensures that only potassium ion can pass through this channel and not other cations like sodium so let’s try to

Understand and let’s look at the extra crystallographic structure of a potassium voltage-gated potassium channel so this is kind of a cartoon depicting the crystallographic structure where we can see the performing domain selectivity filter and the voltage sensor domain and voltage sensor domain as i have mentioned contains several positively charged residue which

Is responsible for the voltage sensing mechanism now let’s try to understand how the selectivity filter works when potassium is present in the environment it is solvated by interacting with several water molecules while it passed through the pores of the kv channel it should have similar kind of interaction and that is provided by the carbonyl ah carbonyl oxygens

Of these voltage sensitive residues so sodium is a smaller cation and it cannot have this optimal interaction and that kind of tells us about the selectivity of potassium channel and that is why sodium cannot pass through but potassium can because all the interactions are optimal with the carbonyl oxygens now let’s try to understand the different states of these

Ion channel there are two alternative states closed state and a open state and the ion channel can switch between these two alternative states notice one thing the voltage sensor is pushed upwards while in the open state and that kind of tells us about the voltage sensitivity of the potassium channel so in the open state the pore is open and potassium can pass

Through this pore now let’s try to understand the getting kinetics by looking at electrophysiological data so under a wholesale wholesale patch clamp configuration we can clamp the voltage into specific magnitudes and record the current here we can hold the voltage at minus 80 millivolt and try to record the current from across these ion channels what we found is

The current is zero at minus 40 the current is still zero at zero millivolts there is some amount of current and the and it increase when we make the voltage more positive and this is how we can get the iv characteristics of voltage-gated potassium channel this tells us the current can be recorded from this ion channel in a relatively positive membrane voltage so

That kind of tells us how this particular ion channel is very selective to a range of voltages but that is the mechanistic aspect but how this is reflecting in terms of physiology in order to understand that let’s try to look at the action potential again but before that let us try to understand what really happens in these voltage ranges at minus 80 millivolt

The inside of the membrane is highly negative so there is a attraction between the positive charge in the voltage sensor and the inside of the membrane that is why the pore is remained in a closed state but in a positive membrane voltage such as 40 millivolt millivolts the inside of the membrane would be positive and there would be a net repulsion between the

Voltage sensitive helix and the inner side of the membrane that would push the helix outwards and that would lead to a open configuration of the potassium channel now we completely understand how voltage sensitivity is allowing channel opening or closing now let’s try to understand the action potential so this is how the molecular events in action potential look

Like we are looking at a small portion of the neural membrane here there is sodium channel voltage sensitive sodium channel in the onset of depolarization voltage sensitive sodium channel opens and sodium ion rushes in that allows the membrane potential to become positive and a lot of membrane potential become positive a lot of sodium ions get in now when the

Membrane potential is becoming positive let’s say at plus 40 millivolt this membrane this voltage sensitive potassium channel starts to open now voltage sensitive potassium channel allows potassium ion to move out of the cell thereby restoring the membrane potential to a negative value again now one thing you should note that these potassium ion channel has a

Slow kinetics so just after the onset of a voltage change they take some time in order of millisecond to conduct the ions and thereby there is a lag in these ion channel conductance probably that is why there is a lag in action potential as well the width of action potential is roughly about a millisecond right okay so this voltage sensitive potassium channel

Can modulate inter-spike interval it can modulate the waveform of action potential it can modulate input resistance and it can overall modulate the excitatory inhibitory balance in a neuronal circuit so in terms of physiology modulation of voltage-gated potassium channel means a lot now several diseases are associated with mutations in these kv channels such as

Epilepsy so generally we have normal uh neuronal activity in the brain but in epilepsy what happens there is a hyper excitability which results in the seizure like symptoms now there are several mutant mutations which are reported in these kv channels namely kv 3.3 where which are associated with epilepsy we can understand why this happens because when we have

When we have less amount of potassium channel or the non-functional potassium channel the repolarization does not take place or takes place at a slower pace that leads to this hyper excitability that leads us to the therapeutic importance of voltage-gated potassium channel modulation so let’s say this is the steady-state firing rate inside our brain when there

Is a change in this firing rate there could be diseases for example hyper excitability occurs in epilepsy or bipolar disorders where there is a increase in the spike frequencies also the decrease in spike frequency occurs in depression or in multiple sclerosis so in these circumstances if we use proper agonist or antagonist of kv channel it might restore the

Firing frequency to a steady state level and it might regain the function that is why these kv channels are really important modulators and therapeutic targets now the potassium current which is recorded from this kv channel has two components within it one is a fast activating and fast inactivating current another is a delayed rectifier current actually there

Are different type of potassium channels which has these characteristic waveforms such as shaker and shell which are mammalian kv-1 and kv-2 family having have these particular kinetics of fast activating and fast inactivating that means their kinetics is relatively fast they opens quickly and they close quickly as well in contrast if we talk about shab or shaw

These names are in drosophila and which which corresponds to kv-3 or kv-4 family all these channels has a relatively uh slower kinetics that means they take more time to close now we can clearly understand how these different ion channels can differentially modulate the action potential waveform or spike frequency moreover one important thing that we should note

The distribution of these kv channels are heterogeneous in different neurons especially kv 1.1 is found throughout the axon whereas kv 2.1 are found in the proximal dendrite kv 4.2 is found in the distal dendrite and kv 3.2 is found all over the dendrites so these differential distribution of voltage-gated potassium channel might imply in terms of their in terms

Of the overall neuronal functionality or signal integration now let me tell you a cool story about the discovery of a voltage-gated potassium channel scientists were looking at fly mutants and they have ems treated multiple mutant lines and their assay was simple they thought since these potassium channels are responsible for modulation of action potential if

There is a mutation in the potassium channel it would lead to a hyper excitability normally a fly is anesthetized under ether exposure and it doesn’t move its legs or any body parts but there are category of mutants which came out of these screen which shows hyper excitability and that is why they shake their legs even under ether anastasia when they are not

Supposed to shake their legs and these mutants are known as shaker mutants the name says it all shaker leg shaking right and that is the discovery of kv-1 family of voltage-gated potassium channel very simple experiment but really elegant now we understand in retrospect that how shaker mutation might have affected the action potential waveform so it might have

Prolonged this repolarization phase and that leads to the hyperexcitability now apart from voltage gated potassium channels there are many other type of potassium channels let me tell you that there are 32 genes in mammals which encode for voltage-gated potassium channels other than voltage-gated potassium channels there would be two transmembrane bromine containing

Inward rectifier channels four transmembrane domain containing two poor domain channels there are slope slow kinetics potassium channel slopes or sk type of potassium channels in different videos we’ll talk about the characteristics of each of these ion channels but let us summarize what we have learned so far we learned the structure of the voltage-gated potassium

Channel opening and closing kinetics distribution of this ion channel and the functional aspect of kv channels if you like this video give it a big thumbs up don’t forget to support me on patreon if you’re an indian viewer you can support me via bmupi your small contribution means a lot for me and my channel my detailed lectures are present in unacademy you can

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Transcribed from video
Voltage gated potassium channels | Activation Cycle of Voltage Gated Potassium Channels By Animated biology With arpan