Researchers have created a cellular probe that combines a tarantula toxin with a fluorescent compound to help scientists observe electrical activity in neurons and other cells. The probe binds to a voltage-activated potassium ion channel subtype, lighting up when the channel is turned off and dimming when it is activated.
This is the first time researchers have been able to visually observe these electrical signalling proteins turn on without genetic modification. These visualization tools are prototypes of probes that could some day help researchers better understand the ion channel dysfunctions that lead to epilepsy, cardiac arrhythmias and other conditions.
The study appears in the Proceedings of the National Academy of Sciences (PNAS) on October 20.
Voltage-gated channels are proteins that allow specific ions, such as potassium or calcium, to flow in and out of cells. They perform a critical function, generating an electrical current in neurons, muscles and other cells. There are many different types, including more than 40 potassium channels. Though other methods can very precisely measure electrical activity in a cell, it has been difficult to differentiate which specific channels are turning on.
The tarantula toxin, guangxitoxin-1E, was an ideal choice because it naturally binds to the Kv2 channels. These channels are expressed in most, if not all, neurons, yet their regulation and activity are complex and actively debated. Sack and his laboratory worked closely with Bruce Cohen, a scientist in the Lawrence Berkeley Lab's Molecular Foundry, who has been studying how fluorescent molecules and nanoparticles can be used to image live cells.
To study the channels, the team engineered variants of tarantula toxin that could be fluorescently labelled and retain function.
These probes were designed to bind to the potassium channels when they were at rest and let go when they became active. The researchers then tested them on living cells. To their surprise, the probes worked right away.