eLife digest | Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels

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Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels

eLife digest

Affiliation details

Harvard University, United States; Howard Hughes Medical Institute, Harvard University, United States

Ion channels are specialized proteins that span the cell membrane. When activated, these channels allow ions to pass through them, which can produce electrical spikes that carry information in nerve cells and regulate the beating of the heart. Researchers interested in understanding how ion channels behave often use a technique called patch clamp electrophysiology to measure the electrical current across the cell membrane. The technique can be used to probe if a specific drug can block an ion channel, but it is not well suited to screening lots of potential drugs because it is slow and expensive.

A group of ion channels known as voltage-gated sodium channels play an important role in generating the electrical spikes in nerve cells. One subtype called NaV1.7 is involved in sensing pain and drugs that block NaV1.7 might be useable as painkillers, but only if they are specific to this channel. This is because there are many similar sodium channels that are important in other processes in the body.

Zhang et al. have now developed a new light-based technique to measure how ion channels behave. The technique uses light to activate the channel and a fluorescent protein to report on the membrane’s voltage. Zhang et al. used the new technique to probe how sodium channels, in particular NaV1.7, interact with drugs. Mammalian cells grown in the lab were engineered to produce NaV1.7, a light-activated ion channel (called CheRiff), and a fluorescent reporter protein. A flash of blue light delivered to the cells activated CheRiff, which in turn activated NaV1.7. At the same time, the fluorescence of the reporter protein was used as a read-out of NaV1.7’s activity.

Zhang et al. showed that they could reproduce many conventional electrophysiology measurements using their new light-based approach. Optical measurements were then used to screen 320 drugs to see whether they could block NaV1.7. The results of the screen corresponded closely with measurements made using conventional electrophysiology. These results demonstrate that the new optical technique is both fast and precise enough to be used in drug discovery. Further studies could now ask if this optical technique can also be used to study other ion channels, such as potassium channels and calcium channels.

DOI: http://dx.doi.org/10.7554/eLife.15202.002