Researchers from SciLifeLab have revealed the activation mechanism of the HCN ion channel by computer simulations, which was also later confirmed in the lab. HCN belongs to an important class of ion channels involved in heartbeat regulation and plays a crucial role in neurons.

Most voltage-gated ion channels are opened by depolarization – which is when the cell membrane potential shifts from negative to positive. HCN ion channels however, are activated by hyperpolarization instead. The HCN voltage sensitive element is called S4 but so far, the mechanism of how it is involved in the activation of the channel is unknown.

“Most electrical signals in your brain are triggered by positive charges entering the cell, but HCN channels are special, as they work in the opposite way, triggered by positive charges exiting the cell. This means they have to work in a totally different way, that we couldn’t have predicted based on ‘standard’ models available so far” says last author Lucie Delemotte (SciLifeLab/KTH).

In a recent study, co-led by SciLifeLab Fellow Lucie Delemotte, researchers identified this novel mechanism by computer simulations which was later confirmed by wet-lab experiments led by Baron Chanda (University of Wisconsin-Madison, USA).

The S4 voltage sensor contains charged amino acids that responds to the electrical stimulus making it change position and subsequently break apart, dividing it into sub-helices which then can drive the channel gate open. This occurs while the rest of the channel architecture remains relatively unaltered and is crucial for the channel to open

The results, published in eLife, provide important information on how this type of ion channels work which in the future could make it possible to modulate their function. The study also demonstrates the power of computer simulations which potentially could cut down research time by years.

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Ok!Read More
Privacy & Cookies Policy

Privacy Overview

This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience.
Necessary
Always Enabled

Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.

Non-necessary

Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.