Researchers discover new photosensitive potassium channel in neurons

Summary: Researchers report that they have identified the first natural photosensitive potassium channel rhodopsins.

Source: Baylor College of Medicine

A key approach to understanding the brain is to observe the behavioral effects of activating specific populations of neurons. One of the most popular approaches to controlling neuronal activity in model systems is called optogenetics and depends on the expression of photosensitive microbial channels in the neurons of interest.

These channels work like light-sensitive switches, turning neurons on with a flash of light, and have been available since 2005. A critical way to confirm the function of neuronal populations would be to repeat the experiment, but this time turning off or on. silencing the same neuronal subpopulations. However, the neuroscience community lacked a quick and powerful way to turn off or silence neurons – until now.

Researchers from the University of Texas Health Sciences Center at Houston McGovern Medical School, Baylor College of Medicine, Rice University and the University of Guelph, Ontario, Canada, reported a new class of light-sensitive channels that promise to pave the way for effective optical neural and silencing.

Posted in Natural neurosciencethe researchers describe how they identified the first natural light-gated potassium (kalium) channel rhodopsins (KCRs).

“A light-activated potassium channel has long been researched as a neuronal silencer, because potassium conductance naturally and universally hyperpolarizes neuronal membranes, terminates action potentials, and returns depolarized neurons to their resting membrane potential,” said the study’s lead author, Dr. John Spudich, Robert A Welch Distinguished Chair in Chemistry at McGovern Medical School.

Using a systematic screen of uncharacterized opsins (proteins that bind to light-reactive chemicals) for their electrophysiological properties, the researchers searched for a rhodopsin-channel with elusive potassium selectivity using a screen patch-clamp photocurrent of opsin-encoding genes with no known function expressed in HEK293 cells.

“Our screening strategy focuses on opsins from organisms that differ in their metabolism and in their habitats from previously studied opsin-containing organisms, and therefore, are more likely to have evolved different opsin functions. adapted to different selective pressures during their evolution,” Spudich said.

“This strategy led us to two opsin-coding genes from the sequenced genome of Hyphochytrium catenoides, a non-photosynthetic heterotrophic mushroom-like protist, both phylogenetically and physiologically distant from algae containing the closely related sodium-selective CCRs. “

“We found that the two H. catenoides channel-rhodopsins – we named HcKCR1 and HcKCR2, for H. catenoides kalium channel-rhodopsins 1 and 2 – were, unlike any other known channel-rhodopsin, highly selective for potassium compared to sodium,” said Dr. Elena Govorunova, associate professor at the Spudich lab and first author.

“In particular, the permeability ratio (PK/PNa) of 23 makes HcKCR1 a potent hyperpolarization tool to suppress firing of excitable neurons upon illumination.”

Dr. Mingshan Xue’s lab at Baylor and the Cain Foundation, Jan and Dan Duncan Neurological Research Institute labs at Texas Children’s Hospital then tested these new tools in neurons.

“When my student Yueyang Gou expressed HcKCR1 in mouse neurons and applied a flash of light, the neurons became electrically silent. This channel overcomes many limitations of previous inhibitors and will be an essential tool to help us understand brain function,” said Xue, Baylor faculty member and co-author of this work.

This shows a neuron
Published in Nature Neuroscience, the researchers describe how they identified the first natural light-gated potassium (kalium) channel rhodopsins (KCRs). Image is in public domain

Graduate student Xiaoyu Lu of Baylor and Rice University’s St-Pierre Laboratory then demonstrated that silence could also be achieved using two-photon excitation, a popular technique for targeting individual neurons in vivo with spatial resolution. – high temporal.

“Two-photon control of KCRs can allow neuroscientists to decipher which neurons are critical for specific behaviors and when their activity is important,” said Dr. François St-Pierre, assistant professor of neuroscience at Baylor and McNair Fellow, and co-author of this work.

“This work is a wonderful example of how multi-institutional collaborations in Houston produce innovative research. Houston is becoming a prime location for the development and application of cutting-edge molecular neurotechnology,” St-Pierre said.

See also

This shows a person's finger zapping a brain with electricity

Going forward, the group will assess the ability of KCRs to silence neurons in vivo and continue to study their biophysical mechanisms to design even better variants. In the long term, they also hope that KCRs could be used in the treatment of potassium channelopathies such as epilepsy, Parkinson’s disease and long QT syndrome and other cardiac arrhythmias.

About this neuroscience research news

Author: Grace Gutierrez
Source: Baylor College of Medicine
Contact: Graciela Gutierrez – Baylor College of Medicine
Image: Image is in public domain

Original research: Access closed.
“Discovery of Long-Sought Photosensitive Potassium Channels: Natural Kalium Channels-Rhodopsins” by John Spudich et al. Natural neuroscience


Summary

Discovery of long-sought photosensitive potassium channels: natural potassium channels-rhodopsins

We report light-sensitive channels in a mushroom-like protist that are highly selective for K+ on Na+.

These microbial rhodopsin channels, called kalium channelrhodopsins, enable robust inhibition of mouse cortical neurons with millisecond precision.

Moreover, the channelrhodopsins of kalium reveal a hitherto unknown mechanism of potassium selectivity.

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