Discovery of second light-activated state in alga ion channel could inform future optogenetics

Researchers have gained new insights into an ion channel from algae. These insights could help optogenetics realize its full potential in the future.

Researchers from Bochum and Regensburg have discovered that a light-sensitive ion channel from the alga Guillardia theta possesses two light-activated states. The newly discovered second state ensures that the ion channel can be reopened particularly quickly after it has been closed.

This makes it interesting for optogenetics, a method researchers use to specifically control the activity of neuronal cells using light. The team from Germany around Dr. Kristin Labudda and Associate Professor Carsten Kötting from the Department of Biophysics at Ruhr University Bochum, as well as Professor Till Rudack from the University of Regensburg, has reported their findings in the journal Communications Biology.

Optogenetics with potential use in therapy

In optogenetics, certain neuronal cells are genetically modified to produce light-sensitive proteins from other organisms. The activity of the modified neuronal cells can then be controlled using light. “When light is directed at these proteins, they alter their structure, thereby activating or inhibiting the cells,” explains Rudack.

Researchers have also been experimenting with optogenetics for the treatment of certain diseases for some time. “Optogenetics is a promising new method, for example, for the treatment of Parkinson’s disease,” says Kötting. “It could reactivate damaged neuronal cells in the brain and partially restore motor skills.”

However, there is still a long way to go before the procedure can potentially be established in everyday clinical practice. Therefore, teams around the world are working to better understand light-sensitive proteins and identify optimal candidates for optogenetics.

One well-studied protein is the ion channel GtACR1 from the alga Guillardia theta, a channelrhodopsin, which serves as a light sensor in the alga. When GtACR1 is activated by light, the channel pore opens, allowing negatively charged ions such as chloride to flow through.

Highly efficient ion channel

In the current study, the researchers from Bochum and Regensburg demonstrated why GtACR1 is so efficient. They examined the ion channel using Fourier transform infrared spectroscopy, which is used to determine the structural states of proteins.

The group demonstrated that GtACR1 has two light-activated states: the well-known ground state and an intermediate stage called the O-intermediate. The ground state is present in the dark.

As with other channelrhodopsins, the normal photocycle starts when the channel is first activated by light. During this cycle, various intermediate stages are passed through, which differ in their structure and ionic conductivity. One of these is the O-intermediate, which precedes the ground state by several seconds.

However, due to the configuration of retinal—the building block that serves as a direct light sensor—the O-intermediate is light-activated in GtACR1, unlike in other channelrhodopsins.

“The second light-activated state we discovered ensures that the channel can be reopened particularly quickly, which significantly increases its ionic conductivity,” explains Labudda. For applications in optogenetics, the higher ionic conductivity means that stimuli can be responded to very precisely and cells can be targeted more specifically. This opens up new possibilities for optogenetic applications.

“With our work, we have discovered a channelrhodopsin with multiple light-activated states for the first time,” summarizes Kötting. “It should be possible to create additional light-activated states in other channelrhodopsins through mutations, thus increasing their effectiveness.

“These findings could pave the way for even more efficient tools in optogenetics—with promising prospects for research and medicine.”