MAR 16, 2016 9:01 AM PDT

Magneto: the Magnetic Field-Responsive Ion Channel

WRITTEN BY: Cassidy Reich
Chemogenetics and optogenetics have been game-changers in neuroscience research. By providing precise control over neural circuits, scientists have been able to use these tools to study behavior and which neurons and circuits are involved in disease in a very in-depth and targeted way. However, as revolutionary as chemogenetics and optogenetics have been, they do have their limitations. Chemogenetics has undesirable kinetics because it takes some time for the injected activator molecule to reach the neurons expressing the receptor and the clearance of the activator molecule can be unpredictable. Optogenetics is much more controlled, but the limitation lies in the fact that light has to reach the neuron being targeted. That makes optogenetics very invasive and limits the ability to study neurons deep in the brain.

Because of how useful but limited these techniques are, a group led by Ali Güler at the University of Virginia have created an ion channel that responds to magnetic fields. The kinetics for this ion channel, obviously dubbed “Magneto,” are fast and controlled, like optogenetics, and using it is noninvasive, like chemogenetics. To build this ion channel, the researchers started with TRPV4, a cation channel that opens in response to stretching of the cell membrane. Exactly how these kinds of mechano-responsive ion channels work is still not known, but it proved to be useful in this construct. To make TRPV4 responsive to magnetic fields, they created a fusion protein with ferritin, an iron storage protein with paramagnetic properties. The idea behind this fusion is that the magnetic field will cause the ferritin to move and pull so that TRPV4 will respond to the pulling by opening and letting Na+ and Ca2+ into the neuron. Below is a schematic of how TRPV4 works normally (a) and how the fusion protein Magneto functions (b).
 

After trial and error and with the addition of a cell membrane-targeting sequence to improve localization and efficacy, the researchers had Magneto. Magneto was tested in multiple models, including mice and zebrafish. Brain slices from mice expressing Magneto in excitatory neurons exhibited rapid neuronal firing in a 50 milliTesla magnetic field and abruptly stopped firing when the magnetic field was turned off. 50 milliTeslas is stronger than a refrigerator magnetic but perfectly safe. For reference, an MRI machine produces a magnetic field between 1 and 3 Teslas. In zebrafish, Magneto was expressed in a specific type of neuron, the Rohon-Beard sensory neurons, which cause the zebrafish larvae to curl up when stimulated. In the presence of a magnetic field, the zebrafish larvae curled up 10 times more often than larvae not in a magnetic field. In another mouse construct, Magneto was expressed in medium spiny neurons in the striatum which are involved in reward behavior. Mice were allowed to explore two chambers, one with a magnetic field and one without. Wild-type mice showed no preference between the two chambers, but the mice expressing Magneto showed a significant preference for the magnetic field chamber. The magnetic field opened Magneto to stimulate the medium spiny neurons which activated a reward circuit that made the mice prefer the magnetic field.

These first experiments with Magneto look very promising, but the group already has ideas for how it can be improved. TRPV4 has ligand binding sites, so one way to improve the specificity of Magneto would be to get rid of these binding sites so that the only thing that could activate Magneto is a magnetic field. Even though Magneto in its current incarnation is a prototype, it has the potential to be a game-changing research tool like optogenetics.

Sources: AlzForum  and Nature Neuroscience
About the Author
Cassidy is a curious person, and her curiosity has led her to pursue a PhD in Pharmacology at the New York University Sackler Institute of Biomedical Sciences. She likes to talk about science way too much, so now she's going to try writing about it.
You May Also Like
AUG 02, 2022
Neuroscience
Could Common Viruses be Triggering Alzheimer's?
AUG 02, 2022
Could Common Viruses be Triggering Alzheimer's?
Recent allegations of research misconduct have called years of Alzheimer's research into question. The controversy surro ...
AUG 15, 2022
Drug Discovery & Development
Electrical Stimulation of Eyes Improves Symptoms of Alzheimer's, Depression
AUG 15, 2022
Electrical Stimulation of Eyes Improves Symptoms of Alzheimer's, Depression
Electrical stimulation of the eye's surface may alleviate depression-like symptoms and improve cognitive function in ...
AUG 28, 2022
Neuroscience
Short Video Clips 'Inoculate' Viewers Against Misinformation
AUG 28, 2022
Short Video Clips 'Inoculate' Viewers Against Misinformation
Brief exposure to short video clips of misinformation strategies improves awareness of online falsehoods. The correspond ...
AUG 29, 2022
Health & Medicine
US-Funded Research to be Open Access by 2026 Under New Federal Guidance
AUG 29, 2022
US-Funded Research to be Open Access by 2026 Under New Federal Guidance
If you have ever done research for school or work, or simply been curious about a scientific finding and wanted to read ...
SEP 05, 2022
Clinical & Molecular DX
Physical Activity May Improve Mental Function in Parkinson's Patients
SEP 05, 2022
Physical Activity May Improve Mental Function in Parkinson's Patients
Parkinson’s disease is a brain disorder that results from the impairment of nerve cells in an area of the brain ca ...
SEP 23, 2022
Genetics & Genomics
Modern Humans Make More Neurons Than Neanderthals
SEP 23, 2022
Modern Humans Make More Neurons Than Neanderthals
Scientists have been searching for an answer to the question of what makes us human for decades. Many have looked to our ...
Loading Comments...