Activation Cycle of Voltage Gated Sodium Channels: Closed, Open, and Inactivated

Voltage gated sodium (Na+) channels are critically important for a variety of neurobiological phenomena, most notably for the Na+ spike action potentials of various neurons. This video discusses the main functional states of voltage gated Na+ channels, focusing on the mechanistic basis for how Na+ channels transition between each state.

[@jonahansen]

Fantastic explication, sir! So much more detail is now known compared to what Hodgkin and Huxley presumed when they first studied the action potential. When I learned this stuff it was clear that there was ion selectivity, voltage gating, etc from the dynamics, but having figured out the molecular mechanism blows my mind. I was always puzzled by how ion selectivity and channel rectification could be produced by molecular structures. People like you, William Catterall, and others have figured it out. Amazing...Kudos!

[@annas9942]

I just started my research related to voltage-gated channels, when I read papers they do not explain the basics very well. So, I came across your video and find it very useful and explanatory.

[@PeteMeighan]

Great to hear this--best of luck to you on your research project!

[@annas9942]

@@PeteMeighan thanks for reply. Same to you!

[@domingopartida5812]

Awesome job with this video, very short and concise

[@yagmurhaciahmetoglu5403]

thank you... you explained it better than my professors!! keep going, you will shine!!

[@PeteMeighan]

Happy to help! Thank you for the kinds words!

[@user-be4md9uf7w]

Thanks for your great video! I will introduce this to my students.

[@ScAymanabdallah]

Great video.. keep going.. and my greeting from Egypt.

[@omnia841]

greetings from Egypt! keep going that video is amazing !

[@Krishna-ub6ij]

Wonderful explanation! Thank you 🙏🏻

[@PeteMeighan]

You're very welcome! Thank you for the kind words.

[@abeerasikandar7077]

Excellent video

[@yz6314]

Wow, what a wonderful explanation, thanks Pete!

[@sonuji14]

Great explanation!

[@PeteMeighan]

Thank you! I'm glad it was helpful!

[@redgrim7708]

Great video!!!

[@PeteMeighan]

Thank you! I appreciate the positive comment. I'm glad you liked the video!

[@scapelplease8273]

Very helpful

[@user-yo9zo8dz8m]

great video from korea

[@My_Channel7]

thanks for your great effort; what is the difference between fast inactivation and slow inactivation?

[@imenehk2048]

WOW THANK YOU!

[@user-ul2sd8yc3g]

This is awesome

[@100.9Ha]

Thanks a lot

[@emiemiriic]

Thank you for this very helpful video! Quick question: When the inactivation gate "activates" - are sodium ions still getting into the pore cavity (and just not through) or do they stay away from the cavity entirely?

[@PeteMeighan]

Thank you for the kind words! It's my understanding this mechanism of inactivation (N-type) does not prevent Na+ ions from entering the channel pore. However, if the binding sites for Na+ in the channel pore are already occupied with Na+ ions, this will prevent additional Na+ ions from accessing the pore. Hope that helps!

[@varisthashaw9368]

Terminology 2 domains- a. voltage sensing domain (positively charged amino acids) b. pore forming domain (outer selectivity filter and inner voltage gate) 3 states a. closed (resting) b. open c. inactivated Concept: the voltage gated sodium channel once opened, needs some time to repolarise. but we cannot allow it to remain open for such a long time because too much sodium would enter the cell. thus there is a need for the inactivation state to exist in between. this state ensures that too much sodium is not entering the cell.

[@paivinmuhammedahmad9039]

Thnx very usefull but i can’t get one thing (can we say when the sodium gated channel is inactivated the cell is in a hyperpolirazation state of action potential?

[@majazahmad4221]

Sir, I am understanding this, please correct me where I go wrong. So closed state is when rmp is there and voltage sensors are attracted inwards and when any stimulus is there , the rmp reverses it's polarity and sensor is attracted outwards and it opens channel and that also leads to relative refractory period right? And when inactivation gate closes that leads to physical absolute refractory period? And one more question, what happens to sodium channel when there is Restless membrane potential?

[@mohamadtarkhan4207]

but how the inactivation gate know when should be open and when should be close? why its exacty one mili second?

[@dannichols6261]

Yes, this is a question I have as well. I've seen a video model which suggests that the opening of the main gate EXPOSES a part of an amino acid which then ATTRACTS the inactivation gate, and similarly when the main gate closes, that movement 'hides' that attractive part, DISRUPTING the attraction and lets the inactivation gate open again (perhaps from Brownian motion of water molecules?), but I'm not sure if that model is correct or not. Need more info. And it's not EXACTLY one millisecond, that's just approximately how long that takes, any where from ~ 0.5 to 1 ms. is what I've read.

[@medicostudy101]

is this applicable to sodium channels in working myocardium? as anti arrythmic application?

[@PeteMeighan]

Absolutely. The principal cardiac Na+ channel (Na.v 1.5) operates similarly with regard to its activation/inactivation/closing mechanisms. Impairments to its activation/deactivation mechanisms can lead to arrhythmia. Many antiarrythmic drugs (e.g., procainamide) target cardiac Na+ channels.

[@samanthawebb3489]

when a neuron is at rest, what do the voltage-gated sodium channels do?

[@PeteMeighan]

Good question! At rest, the voltage gated sodium channels are occupying the "closed" state--ready to transition to the open state and generate an action potential upon depolarization to the threshold potential. Hope that helps!

[@dannichols6261]

@@PeteMeighan Good answer! (It's waiting, basically not doing anything.)

[@luvisacigarette8]

Question: the inactivation gate is essentially the h-gate, correct? And, the m-gate isn't pictured? Thanks for the fantastic visuals and presentation!

[@PeteMeighan]

Thank you so much for the positive comment! Correct about the h-gate. The m-gates basically reflect the positions of the 4 voltage sensors (determining the open probability on a single channel level--or current amplitude on a macroscopic level). Hope that helps. Let me know if you have any additional questions!

[@vidhivora3578]

Woowwww.. ❤️

[@lifeisdeception92]

Allah is the greatest.Every thing is designed so beautifully and for a very defined purpose